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Ocular signs and symptoms of orthokeratology patients associated with povidone iodine-based disinfecting solution

Open AccessPublished:August 02, 2022DOI:https://doi.org/10.1016/j.clae.2022.101742

      Abstract

      Purpose

      To determine the frequency and severity of ocular symptoms and signs in new orthokeratology (ortho-k) subjects using a povidone iodine (PI) disinfecting system compared to those present before lens wear, and whether these were associated with cleaning regimes.

      Methods

      This study recruited 80 subjects from two myopia control studies, who used a PI disinfecting solution for routine use. Ocular symptoms and signs at baseline, one- and six-month after lens wear were reported via questionnaires and ocular examination, respectively. To determine if rates of occurrence were attributable to differences in cleaning regime, subjects were randomly assigned into four groups with respect to routine care procedures, which involved various combinations of rubbing and use of a daily and/or enzymatic cleaner.

      Results

      Sixty-eight subjects completed all aspects of the study. As there were no significant differences in incidence of signs and symptoms between the four groups before and after lens wear (Friedman tests, p > 0.07), data were combined for further analysis. Prior to lens wear, itchiness (69 %) and dryness (53 %) were the most commonly reported symptoms. The frequency and severity of all symptoms remained similar after lens wear (p > 0.10). Presence of follicles in the lower tarsal conjunctiva (22 %) and conjunctival injection (15 %) was frequently observed, but reduced significantly after lens wear (p < 0.01). Mild corneal staining, noted in 13 % of subjects at baseline, did not change significantly over time (p = 0.17). Ocular signs were not necessarily reflected in symptoms and vice versa.

      Conclusion

      Use of a PI-based solution did not increase the frequency or severity of ocular signs and symptoms observed before lens wear. Absence of a difference in occurrence of ocular discomfort with respect to cleaning regimes indicated that the use of the PI-based solution may adequately clean the lenses over a 6-month period.

      Keywords

      1. Introduction

      Contact lens discomfort, defined as ‘a condition characterized by episodic or persistent adverse ocular sensations related to lens wear, either with or without visual disturbance, resulting from reduced compatibility between the contact lens and the ocular environment, which can lead to decreased wearing time and discontinuation of contact lens wear’ [
      • Jones L.
      • Brennan N.A.
      • González-Méijome J.
      • Lally J.
      • Maldonado-Codina C.
      • Schmidt T.A.
      • et al.
      members of the TFOS international workshop on contact lens discomfort. The TFOS international workshop on contact lens discomfort: report of the contact lens materials, design, and care subcommittee.
      ], is an important consideration in contact lens wear [
      • Richdale K.
      • Sinnott L.T.
      • Skadahl E.
      • Nichols J.J.
      Frequency of and factors associated with contact lens dissatisfaction and discontinuation.
      ,
      • Dumbleton K.
      • Woods C.A.
      • Jones L.W.
      • Fonn D.
      The impact of contemporary contact lenses on contact lens discontinuation.
      ]. Several factors have been suggested to be important contributors to such discomfort, including the lens material, care solutions, and biophysical tear film properties [
      • Dumbleton K.
      • Woods C.A.
      • Jones L.W.
      • Fonn D.
      The impact of contemporary contact lenses on contact lens discontinuation.
      ]. Incorporation of surfactants in contact lens solutions, acting as wetting agents and surface cleaners, may reduce discomfort [
      • Jones L.
      • Brennan N.A.
      • González-Méijome J.
      • Lally J.
      • Maldonado-Codina C.
      • Schmidt T.A.
      • et al.
      members of the TFOS international workshop on contact lens discomfort. The TFOS international workshop on contact lens discomfort: report of the contact lens materials, design, and care subcommittee.
      ,
      • Corbin G.S.
      • Bennett L.
      • Espejo L.
      • Carducci S.
      • Sacco A.
      • Hannigan R.
      • et al.
      A multicenter investigation of OPTI-FREE RepleniSH multi-purpose disinfecting solution impact on soft contact lens patient comfort.
      ]. However, most studies investigating discontinuation have focused on conventional soft and RGP contact lenses and adult participants.
      Orthokeratology (ortho-k) is a well-accepted practice to slow the progression of myopia in children [
      • Walline J.J.
      • Jones L.A.
      • Sinnott L.T.
      Corneal reshaping and myopia progression.
      ,
      • Cho P.
      • Cheung S.W.
      Retardation of myopia in orthokeratology (ROMIO) study: a 2-year randomized clinical trial.
      ,
      • Santodomingo-Rubido J.
      • Villa-Collar C.
      • Gilmartin B.
      • Gutierrez-Ortega R.
      Myopia control with orthokeratology contact lenses in Spain: refractive and biometric changes.
      ,
      • Yang B.i.
      • Ma X.
      • Liu L.
      • Cho P.
      Vision-related quality of life of Chinese children undergoing orthokeratology treatment compared to single vision spectacles.
      ,
      • Wang X.
      • Yang B.i.
      • Liu L.
      • Cho P.
      Analysis of parental decisions to use orthokeratology for myopia control in successful wearers.
      ]. However, as this treatment involves the use of rigid lenses, acceptance of a certain degree of discomfort, especially at the commencement of therapy, is necessary for success. Stringent adherence to care procedures is essential as overnight lens wear reduces oxygen tension and tear flow, which can increase the risk of adverse events [
      • Stapleton F.
      Contact lens-related corneal infection in Australia.
      ]. Thus, in contrast to conventional soft and RGP contact lens wear, more frequent monitoring of ocular health and myopia progression are important for successful therapy. During these follow-up visits, review and reinforcement of use and care routines are performed to minimize risks of complications, if necessary. Thus, solutions and other cleaning preparations must be effective not only in removing microorganisms, but also not lead to any ocular symptoms due to irritation or sensitivity. This is especially important for ortho-k lenses, as these are worn overnight and less frequently replaced. As lenses age, scratches and deposit tend to accumulate, increasing attachment of microorganisms and rendering disinfection less effective [
      • Scheuerman T.R.
      • Camper A.K.
      • Hamilton M.A.
      Effects of substratum topography on bacterial adhesion.
      ,
      • Whitehead K.A.
      • Liauw C.M.
      • Lynch S.
      • El Mohtadi M.
      • Amin M.
      • Preuss A.
      • et al.
      Diverse surface properties reveal that substratum roughness affects fungal spore binding.
      ]. In practice, this may be overcome with daily cleaning and regular enzymatic treatment.
      For several years, there had been few advancements in solutions for rigid lenses due to the declining use of conventional rigid lenses, but the increasing popularity of ortho-k, especially in East and South-East Asia, and scleral lenses, has led to revived interest in oxidative care systems [
      • Willcox M.
      • Keir N.
      • Maseedupally V.
      • Masoudi S.
      • McDermott A.
      • Mobeen R.
      • et al.
      CLEAR - Contact lens wettability, cleaning, disinfection and interactions with tears.
      ]. As components of contact lens solutions may contribute to contact lens discomfort [
      • Dumbleton K.
      • Woods C.A.
      • Jones L.W.
      • Fonn D.
      The impact of contemporary contact lenses on contact lens discontinuation.
      ], it is essential that components of these solutions do not cause irritation to the eye. The use of iodine as a disinfectant is well known, acting as an effective oxidative agent [
      • Lambert P.A.
      Mechanisms of action of microbicides.
      ] Whilst its use was reduced due to widely circulated reports of iodine allergy, leading to skin irritation and blistering [
      • Durani P.
      • Leaper D.
      Povidone-iodine: use in hand disinfection, skin preparation and antiseptic irrigation.
      ], several studies have contested the role of iodine in such allergic reactions and attributed the adverse effects to other ingredients added to the medications [
      • Krohne T.U.
      • Allam J.
      • Novak N.
      • Holz F.G.
      “Iodine allergy”: A medical myth with risks for the ophthalmological patient.
      ]. Since the addition of povidone to the formulation, reports of adverse effects have been extremely rare [
      • van Ketel W.G.
      • van den Berg W.H.H.W.
      Sensitization to povidone-iodine.
      ]. Evaluation of toxicity of povidone iodine-based (PI) in the sinonasal and oral cavities reported that PI at concentrations up to 1.25 % could safely be used at these sites for up to five months without any adverse events. PI-based soft contact lens solutions have been available for several years [
      • Martín-Navarro C.M.
      • Lorenzo-Morales J.
      • López-Arencibia A.
      • Valladares B.
      • Piñero J.E.
      Acanthamoeba spp.: efficacy of Bioclen FR One Step, a povidone-iodine based system for the disinfection of contact lenses.
      ] and shown to be effective for disinfection. A study investigating adverse events associated with this solution reported only 0.8 % per 100 participant-months in 40 participants. [
      • Tan J.
      • Datta A.
      • Wong K.
      • Willcox M.D.P.
      • Vijay A.K.
      Clinical outcomes and contact lens case contamination using a povidone–iodine disinfection system.
      ].
      More recently, a rigid lens version of a PI-based lens disinfection solution, cleadewGP (Ophtecs Inc., Japan), was introduced. Its antimicrobial efficacy and ability to kill organisms, including those in established biofilms, and its effect on conjunctival colonization have been reported [
      • Cheung S.W.
      • Boost M.V.
      • Cho P.
      Effect of povidone iodine contact lens disinfecting solution on orthokeratology lens and lens case contamination and organisms in the microbiome of the conjunctiva.
      ,
      • Boost M.V.
      • Cheung S.W.
      • Cho P.
      Investigation of effects of orthokeratology and povidone iodine disinfecting solution on the conjunctival microbiome using MALDI-TOF mass spectrometry.
      ]. In addition to PI, this solution also contains an anionic surfactant, which can remove surface deposits and reduce surface tension, enhancing comfort. Neutralization of PI is achieved via a time-release neutralizing tablet, containing sodium sulfite and a proteolytic enzyme for protein removal. However, the clinical performance of this care system has not been extensively evaluated. This paper reports the frequency and severity of adverse effects over a 6-month period of PI-based solution use in children receiving ortho-k therapy and employing different cleaning regimes.

      2. Methods

      Before commencement of lens wear, subjects (aged 6–10 years old) in two myopia control studies employing ortho-k treatment were also invited to enrol in this study of adverse events. One of these studies was investigating whether addition of 0.01 % atropine to ortho-k therapy enhanced the treatment effect [
      • Tan Q.i.
      • Ng A.LK.
      • Cheng G.PM.
      • Woo V.CP.
      • Cho P.
      Combined atropine with orthokeratology for myopia control: Study design and preliminary results.
      ], so to remove any confounding effect due to atropine use, only subjects receiving ortho-k alone were recruited. The second study merely investigated a minor change in lens design [
      • Guo B.
      • Cheung S.W.
      • Kojima R.
      • Cho P.
      One-year results of the Variation of Orthokeratology Lens Treatment Zone (VOLTZ) study: a prospective randomised clinical trial.
      ], which was not considered likely to have any impact on occurrence of adverse effects. This study received approval from The Hong Kong Polytechnic University (PolyU) (approval number: HSEARS20170430002) and registered at ClinicalTrials.gov (registration number: NCT03193255). Informed consent from the parents and assent from the subjects were obtained before the commencement of study.
      A total of 80 subjects agreed to participate and, before being dispensed with ortho-k lenses (Katt BE free ortho-k lenses; Precision Technology Services, https://www.ptsoptics.com/), were randomized into four groups using different cleaning regimes. All groups disinfected their lenses with the PI-based solution, following the manufacturer’s instructions, with or without cleaning before disinfection. Whilst Group 1 subjects merely disinfected the lenses, the remaining subjects all rubbed their lenses prior to disinfection, of whom Group 3 additionally used a separate daily cleaner (O2 Daily Care Solution; Ophtecs Inc., https://ophtecs.com), Group 4 both a daily cleaner and a weekly protein removal treatment (Progent A + B; Menicon Co, https://www.menicon.com/product/lens-care/), and Group 2 only rubbed their lenses with the PI-based solution as described previously [
      • Martín-Navarro C.M.
      • Lorenzo-Morales J.
      • López-Arencibia A.
      • Valladares B.
      • Piñero J.E.
      Acanthamoeba spp.: efficacy of Bioclen FR One Step, a povidone-iodine based system for the disinfection of contact lenses.
      ]. Before lens insertion, each subject was instructed to rub and rinse their lenses with the Cleadew Dissolving and Rinsing Solution (Ophtecs Inc., https://ophtecs.com) and use unpreserved artificial tears (Teare; Ophtecs Inc., https://ophtecs.com) to cushion the lenses. A similar pre-lens insertion routine is recommended for all ortho-k lens wearers attending the PolyU clinic using other care systems.
      All subjects underwent thorough examinations for vision, ocular assessments at baseline, 1-month, and 6-month visits, and, with assistance from their parents, completed a questionnaire (Appendix A) reporting the frequency and severity of ocular symptoms, including discomfort, dryness, itchiness, burning, visual disturbance, redness, and tearing. The questionnaire was modified from previously validated questionnaires for contact lens wear [
      • Begley C.G.
      • Chalmers R.L.
      • Mitchell G.L.
      • Nichols K.K.
      • Caffery B.
      • Simpson T.
      • et al.
      Characterization of ocular surface symptoms from optometric practices in North America.
      ,
      • Chalmers R.L.
      • Begley C.G.
      • Moody K.
      • Hickson-Curran S.B.
      Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and opinion of contact lens performance.
      ]. It was translated into Chinese and back-translated into English for accuracy by an independent observer. Visual symptoms and symptoms related to lens wear, including discomfort, dryness, itchiness, and burning sensation, redness, and tearing were assessed.

      2.1 Data analysis

      Differences in frequencies and severity of symptoms were evaluated between groups and over time. Kruskal-Wallis test was used to compare the groups at each visit. Friedman tests were used to compare reports of symptoms over the study period. In the absence of significance between groups, data was pooled for the Friedman tests for changes due to lens wear. Chi-squared tests were used to compare symptoms between completed and excluded subjects as well as incidence of symptoms before and after lens wear among the asymptomatic and symptomatic subjects.

      3. Results

      Of the original 80 randomised subjects, one subject withdrew before commencing lens wear. Of the remaining 79 subjects, four did not complete the study, and a further seven failed to complete all questionnaires (see Fig. 1). These 11 subjects were excluded from the final analysis, leaving 68 subjects. There were no differences in the baseline symptoms between the completed and excluded subjects (Chi-squared, 0.91 > p > 0.15). However, data collected from all subjects was included in the descriptive table in Table 1. The mean (SD) age of the subjects was 9.05 (1.14) years, of whom 66 % were female.
      Table 1Frequency of symptoms of the 68 completed and 10 excluded subjects* at the baseline visit.
      Whole dayEnd of day
      AllCompletedExcludedAllCompletedExcluded
      Discomfort
      Never46(59 %)39(57 %)7(70 %)57(73 %)48(71 %)9(90 %)
      Rarely26(33 %)23(34 %)3(30 %)19(24 %)18(26 %)1(10 %)
      Sometimes6(8 %)6(9 %)0(0 %)1(1 %)1(1 %)0(0 %)
      Frequently0(0 %)0(0 %)0(0 %)1(1 %)1(1 %)0(0 %)
      Dryness
      Never38(49 %)32(47 %)6(60 %)54(69 %)47(69 %)7(70 %)
      Rarely28(36 %)25(37 %)3(30 %)20(26 %)18(26 %)2(20 %)
      Sometimes11(14 %)10(15 %)1(10 %)3(4 %)3(4 %)0(0 %)
      Frequently1(1 %)1(1 %)0(0 %)1(1 %)0(0 %)1(10 %)
      Itchiness
      Never28(36 %)21(31 %)7(70 %)37(47 %)32(47 %)5(50 %)
      Rarely18(23 %)16(24 %)2(20 %)23(29 %)19(28 %)4(40 %)
      Sometimes23(29 %)22(32 %)1(10 %)14(18 %)14(21 %)0(0 %)
      Frequently9(12 %)9(13 %)0(0 %)4(5 %)3(4 %)1(10 %)
      Burning
      Never68(87 %)60(88 %)8(80 %)67(86 %)59(87 %)8(80 %)
      Rarely9(12 %)7(10 %)2(20 %)9(12 %)7(10 %)2(20 %)
      Sometimes1(1 %)1(1 %)0(0 %)2(3 %)2(3 %)0(0 %)
      Blurred vision
      Never48(62 %)39(57 %)9(90 %)58(74 %)49(72 %)8(80 %)
      Rarely19(24 %)18(26 %)1(10 %)13(17 %)12(18 %)2(20 %)
      Sometimes8(10 %)8(12 %)0(0 %)6(8 %)6(9 %)0(0 %)
      Frequently2(3 %)2(3 %)0(0 %)0(0 %)0(0 %)0(0 %)
      Constantly1(1 %)1(1 %)0(0 %)1(1 %)1(1 %)0(0 %)
      Redness
      Never61(78 %)53(78 %)8(80 %)
      Rarely11(14 %)9(13 %)2(20 %)
      Sometimes6(8 %)6(9 %)0(0 %)
      Tearing
      Never54(69 %)47(69 %)7(70 %)
      Rarely19(24 %)16(24 %)3(30 %)
      Sometimes4(5 %)4(6 %)0(0 %)
      Frequently1(1 %)1(1 %)0(0 %)
      * One excluded subject did not have baseline questionnaire resulting in 10 excluded subjects at baseline.
      Differences in symptoms between the completed and incomplete subjects were statistically insignificant (Chi-square, 0.91 > p > 0.15).

      3.1 Ocular symptoms

      There were no significant between-group differences either in baseline age and gender, or individual symptoms at any study visit (Kruskal-Wallis tests, 0.95 > p > 0.11) (Table 2), so data from the four groups were combined for further analysis. Although there were no significant changes in frequency or severity of symptoms during the study period (Friedman tests, p > 0.10), analysis of symptoms revealed a variety of patterns, with most subjects remaining consistent, but others experiencing transient periods of discomfort and only a few having more problems at the end of the 6-month study period. An example of this can be seen in the diagrammatic representation of the whole day symptoms for the 39 baseline asymptomatic subjects (Fig. 2). Diagrammatic representation became too complicated for symptomatic subjects with variation of transient improvement and decline, and so are not presented.
      Table 2Frequency of whole day symptoms among the four cleaning groups at baseline, one month and six months of lens wear.
      BaselineFirst monthSixth month
      AllG1G2G3G4AllG1G2G3G4AllG1G2G3G4
      Discomfort
      Never39 (59 %)91110942 (62 %)813101145 (66 %)9121212
      Rarely23 (34 %)465820 (29 %)537516 (24 %)6235
      Sometimes6 (9 %)20316 (9 %)21127 (10 %)0331
      Frequently000000000000000
      Dryness
      Never32 (47 %)6881037 (54 %)69111138 (56 %)7101011
      Rarely25 (37 %)666720 (29 %)346721 (31 %)5673
      Sometimes10 (15 %)33318 (12 %)53006 (9 %)2112
      Frequently1 (1 %)00103 (4 %)11103 (4 %)1002
      Itchiness
      Never21 (31 %)655523 (34 %)673722 (32 %)8446
      Rarely16 (24 %)274327 (40 %)2710824 (35 %)2985
      Sometimes22 (32 %)536813 (19 %)523316 (24 %)4345
      Frequently9 (13 %)22324 (6 %)20206 (9 %)1122
      Constantly000001010000000
      Burning
      Never60 (88 %)1216151755 (81 %)1215141454 (79 %)13161312
      Rarely7 (10 %)312113 (19 %)324410 (15 %)1135
      Sometimes1 (1 %)0010000003 (4 %)1020
      Frequently00010000001 (1 %)0001
      Blurred
      Never39 (57 %)9814846 (68 %)913101444 (65 %)9131111
      Rarely18 (26 %)381618 (26 %)438323 (34 %)6476
      Sometimes8 (12 %)21233 (4 %)11011 (1 %)0001
      Frequently2 (3 %)10101 (1 %)100000000
      Constantly1 (1 %)00010000000000
      Redness
      Never53 (78 %)1015141454 (79 %)1314121549 (72 %)12161011
      Rarely9 (13 %)422111 (16 %)136113 (19 %)2173
      Sometimes6 (9 %)10232 (3 %)10016 (9 %)1014
      Frequently000001 (1 %)000100000
      Tearing
      Never47 (69 %)1113101355 (81 %)1315141350 (74 %)11141015
      Rarely16 (24 %)34638 (12 %)121415 (22 %)2382
      Sometimes4 (6 %)00223 (4 %)00212 (3 %)1001
      Frequently1 (1 %)10001 (1 %)00101 (1 %)1000
      Constantly000001 (1 %)100000000
      G1: Group 1 (N = 15); G2: Group 2 (N = 17); G3: Group 3 (N = 18); G4: Group 4 (N = 18).
      lnsignificant differences in symptoms among the four groups at all study visits (Kruskal-Wallis tests, 0.95 > p > 0.11).
      Figure thumbnail gr2
      Fig. 2Frequencies of whole day discomfort for the 39 subjects who were asymptomatic at baseline (V0), 1-month (V1), and 6-month (V6) visits.
      Table 3 shows data for subjects who did not experience any symptoms before lens wear. For the 39 subjects reporting no ocular discomfort at baseline, as shown in Fig. 2, the majority experienced no discomfort after lens wear and 82 % were symptom-free at the 6-month visit. Similar results were seen for the end-of-day discomfort. With respect to dryness, 31 % of previously asymptomatic subjects experienced dryness after six months of lens wear, although this was reported to occur rarely in eight of these 10 subjects. Somewhat fewer subjects reported problems at the end of the day. Itchiness was the most commonly reported symptom at baseline, with only 21 subjects being asymptomatic. This was also the only symptom that increased significantly after lens wear (Chi-squared, p < 0.001), with almost two-thirds of these previously asymptomatic subjects reporting itchiness at the 6-month visit, seven of whom experienced this sometimes or frequently. This problem was somewhat reduced at the end of the day. Whilst most subjects did not report burning, redness or tearing at baseline, a total of 15 %, 17 %, and 19 %, respectively, reported such problems, mostly occurring rarely, at the 6-month visit.
      Table 3Symptoms reported by subjects, who were asymptomatic at the baseline visit, for the whole day (WD) and at end of day (ED) after one month (M1) and six months (M6) of lens wear.
      Asymptomatic at baselineDiscomfortDrynessItchinessBurningRednessTearingBlurred vision
      WDEDWDEDWDEDWDEDWDWDWDED
      N (% of out 68 subjects)39 (57%)48 (71%)32 (47%)47 (69%)21 (31%)32 (47%)60 (88%)59 (87%)53 (80%)47 (69%)39 (57%)50 (74%)
      (1) No overall change32 (82%)45 (94%)22 (69%)36 (77%)8 (38%)19 (59%)51 (85%)50 (85%)44 (83%)38 (81%)27 (69%)48 (96%)
      Remained asymptomatic25361828613464739332037
      Transient at M1 only7948265355711
      (2) Developed symptoms7 (18%)3 (6%)10 (31%)11 (23%)13 (62%)13 (41%)9 (15%)9 (15%)9 (17%)9 (19%)12 (31%)2 (4%)
      M1 and M6304693114262
      M6 only4365410885760
      Frequency at M6
      Rarely6289688869111
      Sometimes112165113011
      Frequently000110000000
      Severity at M6
      None001200000020
      Very mild638698655871
      Mild101325344031
      Moderate000020000000
      Table 4 shows data for subjects who reported symptoms at baseline. Of these subjects, over half (50–60 %) reported improvement in at least one symptom. For ocular discomfort, 17 out of 29 symptomatic subjects revealed a reduction or no symptom after six months of lens wear. Of the remaining 12 subjects, symptoms of eight were unchanged with only four experiencing symptoms more frequently. Slightly more than half (36/68) of the subjects initially reported dryness, although this appeared to be reduced at the end of the day. Interestingly, 56 % of these subjects reported an improvement in the frequency of experiencing dryness after lens wear, 44 % becoming asymptomatic. Only five subjects reported increased frequency of dryness at the end of the study.
      Table 4Symptoms reported by subjects, who were symptomatic at the baseline visit, for the whole day (WD) and at end of day (ED) after one month (M1) and six months (M6) of lens wear.
      Symptomatic at baselineDiscomfortDrynessItchinessBurningRednessTearingBlurred vision
      WDEDWDEDWDEDWDEDWDWDWDED
      N (% of out 68 subjects)29 (43 %)20 (29 %)36 (53 %)21 (31 %)47 (69 %)36 (53 %)8 (12 %)9 (13 %)15 (20 %)21 (31 %)29 (43 %)18 (26 %)
      (1) Improved17 (59 %)11 (55 %)20 (56 %)13 (62 %)28 (60 %)21 (58 %)4 (50 %)5 (56 %)7 (47 %)14 (67 %)21 (72 %)15 (83 %)
      Asymptomatic at M613916111417345121712
      Improved at M64242144112243
      Frequency at 6 months
      Rarely4242124112143
      Sometimes000020000000
      (2) Remained unchanged8 (28 %)7 (35 %)11 (31 %)5 (24 %)14 (30 %)11 (31 %)1 (13 %)2 (22 %)7 (47 %)5 (24 %)8 (28 %)2 (11 %)
      Frequency at 6 months
      Rarely679565125482
      Sometimes202045002000
      Frequently000041000100
      (3) Deteriorating4 (14 %)2 (10 %)5 (14 %)3 (14 %)5 (10 %)4 (11 %)3 (37 %)2 (22 %)1 (7 %)2 (9 %)01 (6 %)
      Frequency at 6 months
      Sometimes422243221201
      Frequently003111100000
      Severity at 6 months
      Very mild110010000000
      Mild214243321101
      Moderate101101000000
      Itchiness was the most commonly reported symptom of ocular discomfort at baseline, being experienced by 47 (69 %) of the subjects. However, once again, there was an improvement of 60 % after lens wear, with only five reporting more frequent symptoms. Only eight subjects reported a burning sensation before lens wear, of whom four improved. Redness and tearing were initially experienced by 15 (22 %) and 21 (31 %) subjects, respectively, of whom 47 % and 67 % improved, and the symptoms of only one and two subjects, respectively, worsened after lens wear.
      For vision, despite having myopia, 39 (57 %) subjects were happy with their vision at baseline, most of whom had habitual vision aids. Ten of these subjects experienced blurred vision at the 6-month visit, but this rarely occurred in nine. Among the 29 subjects complaining about vision at baseline, 72 % reported improved vision after lens wear and none reported their vision getting worse.

      3.2 Ocular signs

      There were no differences in ocular signs among the four cleaning regimens before and after lens wear (Friedman tests, p > 0.07). Overall, except for follicles in the lower eyelids, very few ocular signs above Grade 1 were observed throughout the study (Table 5). The frequency of corneal staining, which was most often observed in the inferior region, did not change significantly over the study period (Friedman test, p = 0.17). In all cases, this was categorized as Grade 1. The incidence reduced during the early period of lens wear, but returned to somewhat above baseline by the 6-month visit.
      Table 5Ocular signs observed before and after lens wear.
      BaselineMonth 1Month 3Month 6p-value*
      Corneal staining0.17
      Overall9 (13 %)5 (7 %)6 (9 %)12 (18 %)
      Grade 19 (13 %)5 (7 %)6 (9 %)12 (18 %)
      Location
      Central1103
      Inferior6257
      Superior1002
      Nasal1113
      Temporal0202
      Conjunctival injection< 0.001
      Overall10 (15 %)9 (13 %)1 (1 %)1 (1 %)
      Grade 18 (12 %)8 (12 %)00
      Grade 22 (3 %)1 (1 %)1 (1 %)1 (1 %)
      Location
      Inferior1001
      Superior1001
      Nasal10911
      Temporal10911
      Follicles Lower eyelid< 0.01
      Overall15 (22 %)8 (12 %)6 (9 %)7 (10 %)
      Grade 14 (6 %)5 (7 %)3 (4 %)1 (1 %)
      Grade 29 (13 %)2 (3 %)2 (3 %)4 (6 %)
      Grade 3–41 (1 %)1 (1 %)1 (1 %)2 (3 %)
      Location
      Inner central4233
      Tarsal5233
      Lid margin3322
      Nasal5432
      Temporal14867
      * Friedman tests for changes over time.
      Of the 13 % of subjects with conjunctival injection at baseline, only two presented with Grade 2 injection, one of whom reported mild blurry vision after lens wear and the second had no symptoms. Mild conjunctival injection (Grade 1) observed at baseline was not present after three months of lens wear. Two subjects with Grade 2 conjunctival injection at baseline intermittently displayed this sign over the period of lens wear. Follicles were present in the lower eyelid of 22 % subjects at baseline. The prevalence reduced significantly over the study period (Friedman test, p = 0.002). At baseline, 13 % displayed Grade 2 follicles and one subject, Grade 3. Throughout the study period, ocular examination for the presence of follicles revealed clinically significant findings (Grade 3 or above) in only two subjects. One subject with Grade 3 + follicles at baseline, which persisted throughout the period of the study, displayed slight improvement at the 6-month visit, but reported mild itchiness and blurred vision at this time. Follicles were only noted in the second subject at the 6-month visit.

      4. Discussion

      This study evaluated adverse effects associated with the use of a PI-based disinfecting solution for rigid lenses in children undergoing ortho-k treatment. As there was some concern about the advice given by the manufacturer that rubbing of lenses was not required, the study incorporated four cleaning and disinfecting methods, which were randomly allocated to the subjects. Subjects were monitored for a period of six months, with data collection visits after one and six months of lens wear. The results showed that there were no significant differences between the groups with respect to symptoms, indicating that the disinfecting solution adequately removed deposits without additional cleaning steps, probably due to the presence of a surfactant in the solution and/or a proteolytic enzyme incorporated in the neutralizing tablet. However, as deposits do tend to accumulate over time and ortho-k lenses are routinely replaced only on an annual, or even longer, basis, practitioners may wish to err on the side of caution and advise their patients accordingly.
      As there were no significant between-group differences in frequency or severity of symptoms, combined data was used to investigate frequency and severity of symptoms and changes over time. Although ocular discomfort is one of the most frequently reported reasons for contact lens wear discontinuation [
      • Jones L.
      • Brennan N.A.
      • González-Méijome J.
      • Lally J.
      • Maldonado-Codina C.
      • Schmidt T.A.
      • et al.
      members of the TFOS international workshop on contact lens discomfort. The TFOS international workshop on contact lens discomfort: report of the contact lens materials, design, and care subcommittee.
      ], in the current study, there were minimal changes over time in reporting of overall discomfort by 82 % of baseline asymptomatic subjects. This agrees with the findings of previous studies, which reported that serious adverse effects were rarely observed in ortho-k lens wearers [
      • Walline J.J.
      • Jones L.A.
      • Sinnott L.T.
      Corneal reshaping and myopia progression.
      ,
      • Cho P.
      • Cheung S.W.
      • Edwards M.
      The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control.
      ,
      • Kakita T.
      • Hiraoka T.
      • Oshika T.
      Influence of overnight orthokeratology on axial elongation in childhood myopia.
      ,
      • Santodomingo-Rubido J.
      • Villa-Collar C.
      • Gilmartin B.
      • Gutiérrez-Ortega R.
      Orthokeratology vs. spectacles: adverse events and discontinuations.
      ], which may be attributable to ortho-k not involving open eye lens wear, hence not leading to changes to tear film associated with evaporation and incomplete blinking [
      • Nichols J.J.
      • Marsich M.M.
      • Nguyen M.
      • Barr J.T.
      • Bullimore M.A.
      Overnight orthokeratology.
      ,
      • Craig J.P.
      • Willcox M.D.P.
      • Argüeso P.
      • Maissa C.
      • Stahl U.
      • Tomlinson A.
      • et al.
      members of TFOS international workshop on contact lens discomfort. The TFOS international workshop on contact lens discomfort: report of the contact lens interactions with the tear film subcommittee.
      ,
      • Wang X.
      • Li J.
      • Zhang R.
      • Li N.a.
      • Pang Y.i.
      • Zhang Y.
      • et al.
      The influence of overnight orthokeratology on ocular surface and meibomian gland dysfunction in teenagers with myopia.
      ]. In the current study, the majority of subjects had no overall change in symptoms during lens wear, with the exception of itchiness. Most symptoms were reported to occur rarely, with only one subject each reporting dryness or itchiness occurring frequently. The severity of symptoms was generally considered to be mild with moderate severity of itchiness reported by only two subjects (one of whom was the frequent sufferer mentioned above).
      Overall discomfort also improved in 60 % of those subjects symptomatic at baseline. Similar reductions in reporting of individual symptoms also fell by at least 47 % for these subjects (Table 4). A similar reduction in ocular discomfort over a 6-month period of ortho-k lens wear was reported by Wang et al. [
      • Wang X.
      • Li J.
      • Zhang R.
      • Li N.a.
      • Pang Y.i.
      • Zhang Y.
      • et al.
      The influence of overnight orthokeratology on ocular surface and meibomian gland dysfunction in teenagers with myopia.
      ]. However, an extended study [
      • Santodomingo-Rubido J.
      • Villa-Collar C.
      • Gilmartin B.
      • Gutiérrez-Ortega R.
      Orthokeratology vs. spectacles: adverse events and discontinuations.
      ] reported somewhat more adverse effects occurring after six months of lens wear, although not all may have been associated with lens wear. It is possible that wearers become complacent with proper care routines over time and fail to replace lenses as appropriate. Lens deposits can build up, especially in the scratches, on older lenses. Such deposits, if not adequately removed, can take up solution during disinfection, which can leach out during lens wear, increasing the risk for discomfort and solution-induced corneal staining [
      • Lim C.H.L.
      • Stapleton F.
      • Mehta J.S.
      Review of contact lens-related complications.
      ].
      Although dryness was one of the most frequently reported symptoms during lens wear, over 50 % of subjects had reported this problem before commencing treatment. In the majority of these subjects, dryness decreased somewhat over the first month and then remained steady over the rest of the study. Complaints of dryness, the most common reason for discontinuation of soft contact lens wear [
      • Richdale K.
      • Sinnott L.T.
      • Skadahl E.
      • Nichols J.J.
      Frequency of and factors associated with contact lens dissatisfaction and discontinuation.
      ,
      • Dumbleton K.
      • Woods C.A.
      • Jones L.W.
      • Fonn D.
      The impact of contemporary contact lenses on contact lens discontinuation.
      ], were far less frequent, which again may be attributable to the mode of lens wear. The reduction of dryness in initially symptomatic subjects was consistent with the findings of reduced symptoms by Carracedo et al. [
      • Carracedo G.
      • Martin-Gil A.
      • Fonseca B.
      • Pintor J.
      Effect of overnight orthokeratology on conjunctival goblet cells.
      ] whose subjects reported less dryness after changing from silicone hydrogel to ortho-k lens wear. The authors attributed this to an increase in goblet cell density observed after commencing ortho-k lens wear. Such improvement may continue over longer term lens wear (>six months), as a study in China revealed only 23 % of patients reporting dry eye [
      • Wang X.
      • Yang B.i.
      • Liu L.
      • Cho P.
      Analysis of parental decisions to use orthokeratology for myopia control in successful wearers.
      ]. Wang et al. also observed a reduction in reports of dryness after six months of ortho-k lens wear [
      • Wang X.
      • Li J.
      • Zhang R.
      • Li N.a.
      • Pang Y.i.
      • Zhang Y.
      • et al.
      The influence of overnight orthokeratology on ocular surface and meibomian gland dysfunction in teenagers with myopia.
      ]. Their study did report some changes in meibomian gland secretion after commencement of lens wear, but these did not reach significance. Similar to the current study, some subjects had symptoms of dryness at baseline, which worsened after commencement of lens wear. The authors suggested that their subjects may have suffered from mild allergic conjunctivitis, which was aggravated by lens wear [
      • Wang X.
      • Li J.
      • Zhang R.
      • Li N.a.
      • Pang Y.i.
      • Zhang Y.
      • et al.
      The influence of overnight orthokeratology on ocular surface and meibomian gland dysfunction in teenagers with myopia.
      ].
      In the current study, itchiness was the most commonly experienced problem in previously asymptomatic subjects, which was usually mild and infrequent. Over two thirds of the total subjects reported itchiness at baseline, of whom five had increased frequency of symptoms, from rarely to sometimes, or severity, from very mild to mild. Significantly increased itchiness was also reported by new ortho-k wearers in Nanjing, China [
      • Zhao F.
      • Zhao G.
      • Zhao Z.
      Investigation of the effect of orthokeratology lenses on quality of life and behaviors of children.
      ], experienced by 30 % of long-term wearers in Sichuan, China [
      • Wang X.
      • Yang B.i.
      • Liu L.
      • Cho P.
      Analysis of parental decisions to use orthokeratology for myopia control in successful wearers.
      ], and 20 % of patients attending private optometry practices in Hong Kong [
      • Cho P.
      • Cheung S.W.
      • Edwards M.H.
      Practice of orthokeratology by a group of contact lens practitioners in Hong Kong. Part 2: orthokeratology lenses.
      ]. Itchiness is most often associated with the presence of allergens, which may attach to the lens surface and cause problems if lenses are not cleaned adequately. Symptoms can usually be relieved by the use of eye drops, but patients should be reminded to ensure they are correctly caring for their lenses.
      Itchiness may be accompanied by symptoms of burning, redness, and tearing, which can be exacerbated by rubbing the eyes. These symptoms were experienced at baseline by 12 %, 22 %, and 31 %, respectively of subjects, but were reduced after lens wear in over half of these subjects. This may be attributable to the use of eye drops or improved hand hygiene. Interestingly, only a very small number of previously asymptomatic patients reported any of these symptoms after commencement of lens wear. Increased tearing was reported in the Nanjing study [
      • Zhao F.
      • Zhao G.
      • Zhao Z.
      Investigation of the effect of orthokeratology lenses on quality of life and behaviors of children.
      ], but the increase did not reach significance. The prevalence of red eye in long term wearers in Chengdu was 29 % [
      • Wang X.
      • Yang B.i.
      • Liu L.
      • Cho P.
      Analysis of parental decisions to use orthokeratology for myopia control in successful wearers.
      ].
      With regard to vision, of those who had no problems at baseline, 31 % (12/39) reported problems after six months of lens wear with daytime vision, although interestingly, only two of these subjects reported vision problems at the end of the day. Problems with vision would be expected to increase at the end of the day with regression. It is possible that the higher demand of good vision in the classroom led to the complaint of poor daytime vision, which may not be applicable in the smaller home environment in the evening. In addition, the severity was scored as mild or less and, as such, may not be clinically significant (Table 3). For those who reported blurred vision at baseline, the majority reported improvements at six months, with none reporting worsening of symptoms (Table 4). This low level of vision problems is similar to those previously reported by studies on long-term ortho-k wearers [
      • Yang B.i.
      • Ma X.
      • Liu L.
      • Cho P.
      Vision-related quality of life of Chinese children undergoing orthokeratology treatment compared to single vision spectacles.
      ,
      • Wang X.
      • Yang B.i.
      • Liu L.
      • Cho P.
      Analysis of parental decisions to use orthokeratology for myopia control in successful wearers.
      ]. This is to be expected as ortho-k patients are mainly children undergoing therapy for myopia control, whose vision will be carefully monitored and lenses replaced if appropriate [
      • Yang B.i.
      • Ma X.
      • Liu L.
      • Cho P.
      Vision-related quality of life of Chinese children undergoing orthokeratology treatment compared to single vision spectacles.
      ,
      • Wang X.
      • Yang B.i.
      • Liu L.
      • Cho P.
      Analysis of parental decisions to use orthokeratology for myopia control in successful wearers.
      ,
      • Cho P.
      • Tan Q.i.
      Myopia and orthokeratology for myopia control.
      ].
      In contrast to soft contact lens wear, in which symptoms tend to increase over time, leading to reduced wearing time and possible temporary or even permanent discontinuation of lens use [
      • Srinivasan S.
      • Subbaraman L.N.
      The science of contact lens discomfort.
      ], overall symptoms reported in this study tended to reduce over time. This may be attributable to the overnight wear modality. This was reflected in the low number of dropouts in the two parent studies from which the subjects were recruited: after commencement of lens wear, only one subject discontinued due to lens-related problems. Of the initial 80 subjects in this study, one was considered as unsuitable for lens wear during the lens insertion and removal training, and a further three discontinued lens wear during the course of the study. However, only one of these was due to lens discomfort, whilst the second was attributable to persistent poor vision. In general practice, major reasons for discontinuation of ortho-k lens wear are more likely to be cost and inconvenience, rather than adverse effects [
      • Chen Y.-X.
      • Tan Z.
      • He M.-G.
      Who needs myopia control?.
      ,
      • Chan B.
      • Cho P.
      • Cheung S.W.
      Orthokeratology practice in children in a university clinic in Hong Kong.
      ]. Overall discontinuation of ortho-k lens wear is low [
      • Morgan P.B.
      • Efron NATHAN
      • Maldonado-codina CAROLE
      • Efron SUZANNE
      Adverse events and discontinuations with rigid and soft hyper Dk contact lenses used for continuous wear.
      ,
      • Cho P.
      • Cheung S.W.
      • Edwards M.
      The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control.
      ,
      • Kakita T.
      • Hiraoka T.
      • Oshika T.
      Influence of overnight orthokeratology on axial elongation in childhood myopia.
      ,
      • Santodomingo-Rubido J.
      • Villa-Collar C.
      • Gilmartin B.
      • Gutiérrez-Ortega R.
      Orthokeratology vs. spectacles: adverse events and discontinuations.
      ]. However, the cited study is fairly old and newer options for myopia control have been developed in the last decade [
      • Wildsoet C.F.
      • Chia A.
      • Cho P.
      • Guggenheim J.A.
      • Polling J.R.
      • Read S.
      • et al.
      IMI - Interventions Myopia Institute: interventions for controlling myopia onset and progression report.
      ]. This allows transfer to alternative therapies, which tend to be more economical in case of discontinuation of ortho-k treatment.
      Ocular examination revealed few signs. In agreement with most other studies [
      • Chan B.
      • Cho P.
      • Cheung S.W.
      Orthokeratology practice in children in a university clinic in Hong Kong.
      ,
      • Walline J.J.
      • Rah M.J.
      • Jones L.A.
      The Children's Overnight Orthokeratology Investigation (COOKI) pilot study.
      ,
      • Lipson M.J.
      • Sugar A.
      • Musch D.C.
      Overnight corneal reshaping versus soft disposable contact lenses: vision-related quality-of-life differences from a randomized clinical trial.
      ], the frequency of the most commonly reported adverse effect of ortho-k lens wear, corneal staining, varied little over the study period and was very mild in all cases. Santodomingo-Rubido et al. observed that staining occurred most commonly in the central cornea during the early months of ortho-k lens wear and reduced subsequently [
      • Santodomingo-Rubido J.
      • Villa-Collar C.
      • Gilmartin B.
      • Gutiérrez-Ortega R.
      Orthokeratology vs. spectacles: adverse events and discontinuations.
      ]. In contrast, a recent report indicated that corneal staining significantly increased over 2-year ortho-k lens wear [
      • Wang X.
      • Li J.
      • Zhang R.
      • Li N.a.
      • Pang Y.i.
      • Zhang Y.
      • et al.
      The influence of overnight orthokeratology on ocular surface and meibomian gland dysfunction in teenagers with myopia.
      ]. However, in their study, contact lens disinfection was achieved using a care solution containing DMDM hydantoin, which is reported to cause contact allergy in some users and may explain the increase in corneal staining observed. Increased levels of staining have been reported with PHMB-based solutions in soft lens users [
      • Jones L.
      • Jones D.
      • Houlford M.
      Clinical comparison of three polyhexanide-preserved multi-purpose contact lens solutions.
      ], but was not associated with discomfort. It was suggested that PHMB may decrease corneal sensitivity, which may account for the lack of discomfort [
      • Epstein A.B.
      Contact lens care products effect on corneal sensitivity and patient comfort.
      ], although this has not been confirmed by other researchers. One study has suggested that, although there were no differences with respect to discomfort between PHMB- and Polyquad-containing solutions in contact lens wearers, the latter was associated with more corneal staining [
      • Santodomingo-Rubido J.
      The comparative clinical performance of a new polyhexamethylene biguanide- vs a polyquad-based contact lens care regime with two silicone hydrogel contact lenses.
      ]. However, contrary results were reported by several studies [
      • Jones L.
      • Synchyna L.
      Soft contact lens solution review Part 1: components of modern care regimens.
      ,
      • Jones L.
      • Powell C.H.
      Uptake and release phenomena in contact lens care by silicone hydrogel lenses.
      ]. In contrast to solutions containing quaternary ammonium compounds, oxidising solutions lead to less grittiness, dryness, and irritation [
      • Imayasu M.
      • Shiraishi A.
      • Ohashi Y.
      • Shimada S.
      • Cavanagh H.D.
      Effects of multipurpose solutions on corneal epithelial tight junctions.
      ,
      • Lazon de la Jara P.
      • Papas E.
      • Diec J.
      • Naduvilath T.
      • Willcox M.D.
      • Holden B.A.
      Effect of lens care systems on the clinical performance of a contact lens.
      ], as well as reduced levels of corneal staining and corneal infiltrative events [
      • Guillon M.
      • Maissa C.
      • Wong S.
      • Patel T.
      • Garofalo R.
      Effect of lens care system on silicone hydrogel contact lens wettability.
      ].
      As the use of iodine had previously been associated with adverse effects, in particular, irritation and itchiness, this study aimed to determine whether signs and symptoms increased following the commencement of ortho-k lens wear. Tan et al. had reported less staining in adults wearing soft contact lenses using cleadew for soft lenses than patients using other products [
      • Tan J.
      • Datta A.
      • Wong K.
      • Willcox M.D.P.
      • Vijay A.K.
      Clinical outcomes and contact lens case contamination using a povidone–iodine disinfection system.
      ]. They reported no solution-induced staining and significantly better end-of-day comfort, but slightly more low-level itchiness. This agrees with the results of the current study using cleadewGP, indicating that povidone iodine-based solutions are not associated with increased signs and symptoms.
      Cleaning of contact lenses is essential for safe lens wear. Burnham et al. reported problems of cellular debris leading to Pseudomonas adherence to contact lens and storage cases [
      • Burnham G.W.
      • Cavanagh H.D.
      • Robertson D.M.
      The impact of cellular debris on Pseudomonas aeruginosa adherence to silicone hydrogel contact lenses and contact lens storage cases.
      ]. The importance of adherence to routines to avoid adverse effects allows safe use of ortho-k [
      • Walline J.J.
      • Rah M.J.
      • Jones L.A.
      The Children's Overnight Orthokeratology Investigation (COOKI) pilot study.
      ,
      • Mika R.
      • Morgan B.
      • Cron M.
      • Lotoczky J.
      • Pole J.
      Safety and efficacy of overnight orthokeratology in myopic children.
      ]. It has been previously reported that cleadewGP can kill the FDA panel of organisms and significantly reduce levels of Acanthamoeba castellani [
      • Cho P.
      • Reyes S.
      • Boost M.V.
      Microbiocidal characterization of a novel povidone-iodine based rigid contact lens disinfecting solution.
      ], as well as effectively kill organisms present in established biofilms in lens cases [
      • Cho P.
      • Boost M.V.
      Evaluation of prevention and disruption of biofilm in contact lens cases.
      ], thus making cleadewGP an appropriate care solution for ortho-k wearers. Whilst having a strong disinfecting effect on lenses and lens cases, use of the solution did not significantly change the organisms in the ocular microbiome, indicating that it is a safe option. In contrast to PHMB-containing solutions, to which resistance may develop if not correctly used [
      • Shi G.S.
      • Boost M.V.
      • Cho P.
      Does the presence of QAC genes in staphylococci affect the efficacy of disinfecting solutions used by orthokeratology lens wearers?.
      ,
      • Shi G.S.
      • Boost M.V.
      • Cho P.
      Prevalence of antiseptic resistance genes increases in staphylococcal isolates from orthokeratology lens wearers over initial six-month period of use.
      ], as development of resistance to iodine has not been reported, loss of effectiveness is unlikely to occur.
      Follicles, which were present in the subjects at baseline, are a common occurrence in children of Chinese ethnicity, as 33 % of children aged 6–15 years, who did not wear contact lenses, were found to have follicles in the lower lids [
      • Chan K.Y.
      • Cho P.
      • Chan Y.Y.
      • Cheung S.W.
      • Swann P.G.
      Prevalence of papillary changes and folliculosis of the palpebral conjunctiva in asymptomatic Chinese children.
      ]. The prevalence of follicles tends to decrease over time [
      • Chan K.Y.
      • Cho P.
      • Chan Y.Y.
      • Cheung S.W.
      • Swann P.G.
      Prevalence of papillary changes and folliculosis of the palpebral conjunctiva in asymptomatic Chinese children.
      ] and this was also observed in the current study. Of the two subjects with Grade 3 follicles at baseline, their presence was persistent at all visits for one subject, whilst for the second, were absent at 1-month and 3-month, but returned at the 6-month visit. Both subjects had no self-reported symptoms at any visit. It is thought that follicles may be related to developing immunity in young children [
      • Chan K.Y.
      • Cho P.
      • Chan Y.Y.
      • Cheung S.W.
      • Swann P.G.
      Prevalence of papillary changes and folliculosis of the palpebral conjunctiva in asymptomatic Chinese children.
      ].
      A major limitation of this study was that it could not be extended beyond six months, although it is recognized that the development of signs and symptoms may occur more frequently if the originally prescribed lens is still in use after this time. This is most often due to build-up of lens deposits and scratches on the lens surface. However, for many subjects, their lenses would have been replaced by this time due to damage, scratches, and changes in prescription, as the subjects were recruited from myopia control studies. Nevertheless, as the major issue with povidone iodine-based solution is the perception that iodine may be an irritant, the results strongly indicate that there were no significant adverse effects with its use and were comparable or superior to use of other care systems. Sample size for the current study was relatively small and this may have prevented detection of differences between cleaning regimes. However, comparison of each of the five elements examined each on three occasions revealed that none of the differences between groups reached significance and, interestingly, the highest frequency of symptoms was seen in the groups using the more intensive cleaning regimes. This study did not include a control group using an alternative disinfecting solution. The side effects of other systems, especially PHMB-based and hydrogen peroxide, have been investigated and reported in a number of published papers. Hence, to avoid repetition and to enable recruitment of an adequate sample size, a case series design was adopted.
      In conclusion, this study showed that the use of cleadewGP, a PI-based disinfecting solution, did not lead to any increase in overall ocular discomfort and little or no change in both signs and symptoms, suggesting it is suitable as a disinfecting solution for ortho-k or other rigid lenses. For ortho-k wear to be successful, it needs to be not only effective for myopia control, it also has to be safe and comfortable. Different cleaning regimes did not appear to affect the frequency and severity of signs and symptoms of ortho-k wearers, which may be attributable to the inclusion of a surfactant and an enzymatic cleaner. However, as this was a fairly short-term study observing only the first 6-month of lens wear, it may not reflect longer term use, especially if the lenses are not replaced regularly.

      Funding

      This study is an outcome from a Collaborative Research Agreement between The Hong Kong Polytechnic University and Ophtecs Corporation, Japan (Grant No H-ZG5G).

      6. Commercial relationship

      The authors have declared that no commercial relationship with any products used in this report.

      Declaration of Competing Interest

      The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

      Acknowledgements

      This study was sponsored by a Collaborative Research Agreement between The Hong Kong Polytechnic University and Ophtecs Corporation, Japan (Grant number H-ZG5G).

      Appendix A

      Have you experienced the following problems during a typical day in the past 2 weeks? Please circle the most appropriate answer.
      Tabled 1
      01234
      FrequencyNeverRarelySometimesFrequentlyConstantly
      SeverityNoneVery MildMildModerateSevere
      Tabled 1
      1. How often did your eyes fell discomfort? When your eyes felt discomfort, how intense was this feeling of discomfort?
      Whole DayEnd of Day (before insertion)
      Frequency0 1 2 3 4Frequency0 1 2 3 4
      Severity0 1 2 3 4Severity0 1 2 3 4
      2. How often did your eyes fell discomfort? When your eyes felt discomfort, how intense was this feeling of discomfort?
      Whole DayEnd of Day (before insertion)
      Frequency0 1 2 3 4Frequency0 1 2 3 4
      Severity0 1 2 3 4Severity0 1 2 3 4
      3. How often did your eyes fell itchy? When your eyes felt itchy, how intense was this feeling of itching?
      Whole DayEnd of Day (before insertion)
      Frequency0 1 2 3 4Frequency0 1 2 3 4
      Severity0 1 2 3 4Severity0 1 2 3 4
      4. How often did your eyes fell burning and stinging? When your eyes felt burning and stinging, how intense was this feeling of burning and stinging?
      Whole DayEnd of Day (before insertion)
      Frequency0 1 2 3 4Frequency0 1 2 3 4
      Severity0 1 2 3 4Severity0 1 2 3 4
      5. How often did your vision change between clear and blurry or foggy? When your vision was blurry, how noticeable was the changeable, blurry or fogging vision? □ with glasses □ without glasses
      Whole DayEnd of Day (before insertion)
      Frequency0 1 2 3 4Frequency0 1 2 3 4
      Severity0 1 2 3 4Severity0 1 2 3 4
      6. How often did your eyes look red? When your eyes were red, how much did the red eyes bother you?
      Whole DayEnd of Day (before insertion)
      Frequency0 1 2 3 4Frequency0 1 2 3 4
      Severity0 1 2 3 4Severity0 1 2 3 4
      7. How often did your eyes look or feel excessively watering? When your eyes were watery, how much did the watery eyes bother you?
      Whole DayEnd of Day (before insertion)
      Frequency0 1 2 3 4Frequency0 1 2 3 4
      Severity0 1 2 3 4Severity0 1 2 3 4

      References

        • Jones L.
        • Brennan N.A.
        • González-Méijome J.
        • Lally J.
        • Maldonado-Codina C.
        • Schmidt T.A.
        • et al.
        members of the TFOS international workshop on contact lens discomfort. The TFOS international workshop on contact lens discomfort: report of the contact lens materials, design, and care subcommittee.
        Invest Ophthalmol Vis Sci. 2013; 54: TFOS37
        • Richdale K.
        • Sinnott L.T.
        • Skadahl E.
        • Nichols J.J.
        Frequency of and factors associated with contact lens dissatisfaction and discontinuation.
        Cornea. 2007; 26: 168-174
        • Dumbleton K.
        • Woods C.A.
        • Jones L.W.
        • Fonn D.
        The impact of contemporary contact lenses on contact lens discontinuation.
        Eye Contact Lens. 2013; 39: 93-99
        • Corbin G.S.
        • Bennett L.
        • Espejo L.
        • Carducci S.
        • Sacco A.
        • Hannigan R.
        • et al.
        A multicenter investigation of OPTI-FREE RepleniSH multi-purpose disinfecting solution impact on soft contact lens patient comfort.
        Clin Ophthalmol. 2010; 4: 47-57
        • Walline J.J.
        • Jones L.A.
        • Sinnott L.T.
        Corneal reshaping and myopia progression.
        Br J Ophthalmol. 2009; 93: 1181-1185
        • Cho P.
        • Cheung S.W.
        Retardation of myopia in orthokeratology (ROMIO) study: a 2-year randomized clinical trial.
        Invest Ophthalmol Vis Sci. 2012; 53: 7077-7085
        • Santodomingo-Rubido J.
        • Villa-Collar C.
        • Gilmartin B.
        • Gutierrez-Ortega R.
        Myopia control with orthokeratology contact lenses in Spain: refractive and biometric changes.
        Invest Ophthalmol Vis Sci. 2012; 53: 5060-5065
        • Yang B.i.
        • Ma X.
        • Liu L.
        • Cho P.
        Vision-related quality of life of Chinese children undergoing orthokeratology treatment compared to single vision spectacles.
        Cont Lens Anterior Eye. 2021; 44: 101350
        • Wang X.
        • Yang B.i.
        • Liu L.
        • Cho P.
        Analysis of parental decisions to use orthokeratology for myopia control in successful wearers.
        Ophthalmic Physiol Opt. 2021; 41: 3-12
        • Stapleton F.
        Contact lens-related corneal infection in Australia.
        Clin Exp Optom. 2020; 103: 408-417
        • Scheuerman T.R.
        • Camper A.K.
        • Hamilton M.A.
        Effects of substratum topography on bacterial adhesion.
        J Colloid Interface Sci. 1998; 208: 23-33
        • Whitehead K.A.
        • Liauw C.M.
        • Lynch S.
        • El Mohtadi M.
        • Amin M.
        • Preuss A.
        • et al.
        Diverse surface properties reveal that substratum roughness affects fungal spore binding.
        iScience. 2021; 24: 102333
        • Willcox M.
        • Keir N.
        • Maseedupally V.
        • Masoudi S.
        • McDermott A.
        • Mobeen R.
        • et al.
        CLEAR - Contact lens wettability, cleaning, disinfection and interactions with tears.
        Cont Lens Anterior Eye. 2021; 44: 157-191
        • Lambert P.A.
        Mechanisms of action of microbicides.
        in: Fraise A.P. Maillard J. Sattar S. Russell, Hugo and Ayliffe's Principles and Practice of Disinfection, Preservation and Sterilization. 5th Edition. Somerset, Wiley-Blackwell2013: 95-107
        • Durani P.
        • Leaper D.
        Povidone-iodine: use in hand disinfection, skin preparation and antiseptic irrigation.
        Int Wound J. 2008; 5: 376-387
        • Krohne T.U.
        • Allam J.
        • Novak N.
        • Holz F.G.
        “Iodine allergy”: A medical myth with risks for the ophthalmological patient.
        Ophthalmologe. 2016; 113: 1023-1028
        • van Ketel W.G.
        • van den Berg W.H.H.W.
        Sensitization to povidone-iodine.
        Dermatol Clin. 1990; 8: 107-110
        • Martín-Navarro C.M.
        • Lorenzo-Morales J.
        • López-Arencibia A.
        • Valladares B.
        • Piñero J.E.
        Acanthamoeba spp.: efficacy of Bioclen FR One Step, a povidone-iodine based system for the disinfection of contact lenses.
        Exp Parasitol. 2010; 126: 109-112
        • Tan J.
        • Datta A.
        • Wong K.
        • Willcox M.D.P.
        • Vijay A.K.
        Clinical outcomes and contact lens case contamination using a povidone–iodine disinfection system.
        Eye Contact Lens. 2018; 44: S221-S227
        • Cheung S.W.
        • Boost M.V.
        • Cho P.
        Effect of povidone iodine contact lens disinfecting solution on orthokeratology lens and lens case contamination and organisms in the microbiome of the conjunctiva.
        Cont Lens Anterior Eye. 2021; 44: 101412
        • Boost M.V.
        • Cheung S.W.
        • Cho P.
        Investigation of effects of orthokeratology and povidone iodine disinfecting solution on the conjunctival microbiome using MALDI-TOF mass spectrometry.
        Adv Ophthalmol Pract Res. 2021; 1: 100024
        • Tan Q.i.
        • Ng A.LK.
        • Cheng G.PM.
        • Woo V.CP.
        • Cho P.
        Combined atropine with orthokeratology for myopia control: Study design and preliminary results.
        Curr Eye Res. 2019; 44: 671-678
        • Guo B.
        • Cheung S.W.
        • Kojima R.
        • Cho P.
        One-year results of the Variation of Orthokeratology Lens Treatment Zone (VOLTZ) study: a prospective randomised clinical trial.
        Ophthalmic Physiol Opt. 2021; 41: 702-714
        • Begley C.G.
        • Chalmers R.L.
        • Mitchell G.L.
        • Nichols K.K.
        • Caffery B.
        • Simpson T.
        • et al.
        Characterization of ocular surface symptoms from optometric practices in North America.
        Cornea. 2001; 20: 610-618
        • Chalmers R.L.
        • Begley C.G.
        • Moody K.
        • Hickson-Curran S.B.
        Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and opinion of contact lens performance.
        Optom Vis Sci. 2012; 89: 1435-1442
        • Cho P.
        • Cheung S.W.
        • Edwards M.
        The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a pilot study on refractive changes and myopic control.
        Curr Eye Res. 2005; 30: 71-80
        • Kakita T.
        • Hiraoka T.
        • Oshika T.
        Influence of overnight orthokeratology on axial elongation in childhood myopia.
        Invest Ophthalmol Vis Sci. 2011; 52: 2170-2174
        • Santodomingo-Rubido J.
        • Villa-Collar C.
        • Gilmartin B.
        • Gutiérrez-Ortega R.
        Orthokeratology vs. spectacles: adverse events and discontinuations.
        Optom Vis Sci. 2012; 89: 1133-1139
        • Nichols J.J.
        • Marsich M.M.
        • Nguyen M.
        • Barr J.T.
        • Bullimore M.A.
        Overnight orthokeratology.
        Optom Vis Sci. 2000; 77: 252-259
        • Craig J.P.
        • Willcox M.D.P.
        • Argüeso P.
        • Maissa C.
        • Stahl U.
        • Tomlinson A.
        • et al.
        members of TFOS international workshop on contact lens discomfort. The TFOS international workshop on contact lens discomfort: report of the contact lens interactions with the tear film subcommittee.
        Invest Ophthalmol Vis Sci. 2013; 54: TFOS123
        • Wang X.
        • Li J.
        • Zhang R.
        • Li N.a.
        • Pang Y.i.
        • Zhang Y.
        • et al.
        The influence of overnight orthokeratology on ocular surface and meibomian gland dysfunction in teenagers with myopia.
        J Ophthalmol. 2019; 2019: 1-6
        • Lim C.H.L.
        • Stapleton F.
        • Mehta J.S.
        Review of contact lens-related complications.
        Eye Contact Lens. 2018; 44: S1-S
        • Carracedo G.
        • Martin-Gil A.
        • Fonseca B.
        • Pintor J.
        Effect of overnight orthokeratology on conjunctival goblet cells.
        Cont Lens Anterior Eye. 2016; 39: 266-269
        • Zhao F.
        • Zhao G.
        • Zhao Z.
        Investigation of the effect of orthokeratology lenses on quality of life and behaviors of children.
        Eye Contact Lens. 2018; 44: 335-338
        • Cho P.
        • Cheung S.W.
        • Edwards M.H.
        Practice of orthokeratology by a group of contact lens practitioners in Hong Kong. Part 2: orthokeratology lenses.
        Clin Exp Optom. 2003; 86: 42-46
        • Srinivasan S.
        • Subbaraman L.N.
        The science of contact lens discomfort.
        Rev Optom. 2015; : 34-39
        • Cho P.
        • Tan Q.i.
        Myopia and orthokeratology for myopia control.
        Clin Exp Optom. 2019; 102: 364-377
        • Chen Y.-X.
        • Tan Z.
        • He M.-G.
        Who needs myopia control?.
        Int J Ophthalmol. 2021; 14: 1297-1301
        • Chan B.
        • Cho P.
        • Cheung S.W.
        Orthokeratology practice in children in a university clinic in Hong Kong.
        Clin Exp Optom. 2008; 91: 453-460
        • Morgan P.B.
        • Efron NATHAN
        • Maldonado-codina CAROLE
        • Efron SUZANNE
        Adverse events and discontinuations with rigid and soft hyper Dk contact lenses used for continuous wear.
        Optom Vis Sci. 2005; 82: 528-535
        • Wildsoet C.F.
        • Chia A.
        • Cho P.
        • Guggenheim J.A.
        • Polling J.R.
        • Read S.
        • et al.
        IMI - Interventions Myopia Institute: interventions for controlling myopia onset and progression report.
        Invest Ophthalmol Vis Sci. 2019; 60: M106-M311
        • Walline J.J.
        • Rah M.J.
        • Jones L.A.
        The Children's Overnight Orthokeratology Investigation (COOKI) pilot study.
        Optom Vis Sci. 2004; 81: 407-413
        • Lipson M.J.
        • Sugar A.
        • Musch D.C.
        Overnight corneal reshaping versus soft disposable contact lenses: vision-related quality-of-life differences from a randomized clinical trial.
        Optom Vis Sc. 2005; 82: 886-891
        • Jones L.
        • Jones D.
        • Houlford M.
        Clinical comparison of three polyhexanide-preserved multi-purpose contact lens solutions.
        Cont Lens Anterior Eye. 1997; 20: 23-30
        • Epstein A.B.
        Contact lens care products effect on corneal sensitivity and patient comfort.
        Eye Contact Lens. 2006; 32: 128-132
        • Santodomingo-Rubido J.
        The comparative clinical performance of a new polyhexamethylene biguanide- vs a polyquad-based contact lens care regime with two silicone hydrogel contact lenses.
        Ophthalmic Physiol Opt. 2007; 27: 168-173
        • Jones L.
        • Synchyna L.
        Soft contact lens solution review Part 1: components of modern care regimens.
        Optom Pract. 2007; 8: 45-56
        • Jones L.
        • Powell C.H.
        Uptake and release phenomena in contact lens care by silicone hydrogel lenses.
        Eye Contact Lens. 2013; 39: 29-36
        • Imayasu M.
        • Shiraishi A.
        • Ohashi Y.
        • Shimada S.
        • Cavanagh H.D.
        Effects of multipurpose solutions on corneal epithelial tight junctions.
        Eye Contact Lens. 2008; 34: 50-55
        • Lazon de la Jara P.
        • Papas E.
        • Diec J.
        • Naduvilath T.
        • Willcox M.D.
        • Holden B.A.
        Effect of lens care systems on the clinical performance of a contact lens.
        Optom Vis Sci. 2013; 90: 344-350
        • Guillon M.
        • Maissa C.
        • Wong S.
        • Patel T.
        • Garofalo R.
        Effect of lens care system on silicone hydrogel contact lens wettability.
        Cont Lens Anterior Eye. 2015; 38: 435-441
        • Burnham G.W.
        • Cavanagh H.D.
        • Robertson D.M.
        The impact of cellular debris on Pseudomonas aeruginosa adherence to silicone hydrogel contact lenses and contact lens storage cases.
        Eye Contact Lens. 2012; 38: 7-15
        • Mika R.
        • Morgan B.
        • Cron M.
        • Lotoczky J.
        • Pole J.
        Safety and efficacy of overnight orthokeratology in myopic children.
        Optometry. 2007; 78: 225-231
        • Cho P.
        • Reyes S.
        • Boost M.V.
        Microbiocidal characterization of a novel povidone-iodine based rigid contact lens disinfecting solution.
        Cont Lens Anterior Eye. 2018; 41: 542-546
        • Cho P.
        • Boost M.V.
        Evaluation of prevention and disruption of biofilm in contact lens cases.
        Ophthalmic Physiol Opt. 2019; 39: 337-349
        • Shi G.S.
        • Boost M.V.
        • Cho P.
        Does the presence of QAC genes in staphylococci affect the efficacy of disinfecting solutions used by orthokeratology lens wearers?.
        Br J Ophthalmol. 2016; 100: 708-712
        • Shi G.S.
        • Boost M.V.
        • Cho P.
        Prevalence of antiseptic resistance genes increases in staphylococcal isolates from orthokeratology lens wearers over initial six-month period of use.
        Eur J Clin Microbiol Infect Dis. 2016; 35: 955-962
        • Chan K.Y.
        • Cho P.
        • Chan Y.Y.
        • Cheung S.W.
        • Swann P.G.
        Prevalence of papillary changes and folliculosis of the palpebral conjunctiva in asymptomatic Chinese children.
        Cont Lens Anterior Eye. 2013; 36: 62-65