The safety of orthokeratology in myopic children and analysis of related factors.

OBJECTIVE: To evaluate the safety of overnight orthokeratology (OK) wear and explore whether factors such as age, refraction and allergic conjunctivitis (AC) history were associated with corneal adverse events (AEs) incidence. METHODS: Medical records of consecutive patients who started OK for myopia correction and continued for more than one year were retrospectively reviewed. Clinical data including sex, baseline age, spherical equivalent refraction (SER), and related medical histories were retrieved. A total of 489 eyes from 260 patients (age: 8-15 years; SER: -1.00 to -6.00 D) were included. Corneal adverse events were the primary outcome. The generalized estimating equations model was used to evaluate the effects of sex, age, SER, and allergic conjunctivitis history on corneal AE incidence over the one-year period. RESULTS: A total of 111 eyes (22.7%) had corneal AE during the one-year follow-up (corneal staining [n = 106], corneal infiltration [n = 5]) and the incidence of significant AE was 6.9%. The corneal AE incidence was associated with age (OR = 0.874, 95%CI = 0.781-0.978, p = 0.019); SER (OR=0.632, 95%CI=0.531-0.754, p < 0.001); and AC (OR=1.706, 95%CI=1.017-2.860, p = 0.043). High refraction was the key risk factor for significant AE (OR=0.542, 95%CI=0.401-0.732, p < 0.001). CONCLUSIONS: Orthokeratology is a safe option for children with myopia. Younger age, higher myopia, and AC were risk factors for corneal AE in OK wearers. Whereas, only higher myopia was a risk factor for significant AE.

[The Influence of Short-term Orthokeratology on Tear Film in Adult Myope].

OBJECTIVE: To study the changes of tear film after short-term overnight orthokeratology wearing in adult myope. METHODS: Fifty adult myope aged 18 to 38 years old were enrolled in this study. The patients wore orthokeratology 6-10 h every night during this study. Data such as non-invasive tear break-up time (NITBUT), fluorescent tear break-up time (FTBUT), lower tear meniscus height (LTMH), corneal fluorescent staining as well as ocular surface disease index (OSDI) questionnaire score were measured at baseline, 1 d, 7 d, 14 d, 30 d and 90 d. RESULTS: Forty-four subjects completed the follow-up study. Tear break-up time (TBUT) decreased and became stable at 14 d after overnight orthokeratology wearing. LTMH sustained decreased and there was a difference after 90 d overnight wearing （ P<0.05）. Compared with baseline, the grade of corneal staining increased at all time points （ P<0.05）. As for the OSDI score, there was no difference at all time points. CONCLUSION: After overnight orthokeratology wearing, tear film stability and tear secretion decreased. Adult myope seems easily to suffer corneal injury after overnight orthokeratology wearing.

The Effect of Treatment Zone Decentration on Myopic Progression during Or-thokeratology.

Purpose: To evaluate the relationship between magnitude of orthokeratology (OrthoK) treatment zone decentration and 2-year axial length (AL) elongation in myopic children.Methods: One-hundred and one Chinese children who wore OrthoK contact lenses for 2 years. The magnitude and direction of the OrthoK treatment zone center from the entrance pupil center were recorded after 3 and 24 months of lens wear along with AL measurement. Stepwise multiple linear regression analysis was performed to assess which factors significantly affected an increase in AL.Results: After 3 and 24 months of OrthoK treatment, the mean (± standard deviation [SD]) magnitude of the OrthoK treatment zone decentration was 0.64 ± 0.38 mm and 0.68 ± 0.32 mm, respectively. There were no significant differences between the two time points (P > .05). After 2 years of OrthoK contact lenses wear, the mean (± SD) AL growth was 0.36 ± 0.34 mm. The axial elongation was slightly correlated with baseline age of subjects (r = -0.073, P < .001), baseline spherical equivalent refractive error (r = -0.088, P < .001) and magnitude decentration of treatment zone (r = -0.190, P = .027).Conclusions: The decentration of OrthoK treatment zone stabilizes after 3 months of lens wear and slightly decreases AL growth.

Corneal epithelial and stromal thickness changes in myopic orthokeratology and their relationship with refractive change.

PURPOSE: To investigate topographic changes in corneal epithelial thickness (CET) and stromal thickness following orthokeratology (OK) and to determine associated factors affecting refractive changes. METHODS: This study investigated the topographic changes in CET and stromal thickness in 60 myopic eyes that were fitted with OK lenses. CET and stromal thickness were obtained using spectral-domain optical coherence tomography (OCT) before and after OK lens wear. Changes in refractive error and corneal topography data were obtained. The correlation between refractive change and corneal thickness change, and various refractive, lens, and topographic parameters were analyzed using simple regression analysis. RESULTS: Mean refractive error changed by 1.75 ± 0.79 diopters (D). The mean CET of the center zone (2 mm in diameter), paracenter (2 to 5 mm annular ring: 1 to 2.5 mm from center), and mid-periphery (5 to 6 mm annular ring: 2.5 to 3 mm from center) changed by -8.4, -1.4, and +2.7 µm, respectively, after OK lens wear. There was an increase of 2.0, 3.3, and 3.9 µm, respectively, in the center, paracenter, and mid-periphery of the stroma. A larger refractive correction was associated with a flatter base curve of the lens, larger decrease in the central epithelium, and smaller treatment diameter in corneal topography. CONCLUSION: OK lenses caused the central corneal epithelium to thin while the mid-peripheral epithelium and stroma became thicker. Refractive changes during OK are associated with changes in central epithelial thickness, while stromal changes did not contribute significantly.

Assessment of Tear Film and Bulbar Redness by Keratograph 5M in Pediatric Patients After Orthokeratology.

OBJECTIVES: To assess the tear meniscus height (TMH), noninvasive tear breakup time (NITBUT), and bulbar redness in pediatric patients after orthokeratology (OK). METHODS: Pediatric patients who underwent overnight OK between December 2014 and November 2017 were retrospectively investigated. According to the time of wearing, subjects were divided into three groups: 1-week, 1-month, and over 1-year. Age-matched subjects were recruited as a control group. Keratograph 5M was used to assess TMH, NITBUT-first, NITBUT-average, and bulbar redness score. RESULTS: A total of 106 subjects aged from 7 to 15 years were included. Compared with control group, NITBUT-first was significantly lower in 1-week group (P=0.036) and NITBUT-average was significantly lower in 1-month group (P=0.019). Compared with over 1-year group, NITBUT-first was significantly lower in 1-week and 1-month groups (P=0.014, P=0.035, respectively), and NITBUT-average was significantly lower in 1-month group (P=0.022). Bulbar redness score was significantly lower in 1-month group than 1-week group (P=0.004). No significant difference in TMH was found between all groups. Significant correlation was found between NITBUT-first and NITBUT-average in all subjects (R=0.812, P<0.001). No other significant correlations were found between variables included TMH, NITBUT, bulbar redness score, or target correction. CONCLUSIONS: As a noninvasive method, Keratograph 5M was easily to be applied on pediatric patients. The OK lens did not induce significant tear deficiency or bulbar redness, but might affect tear film stability in a short term after wearing.

MiSight Assessment Study Spain: Adverse Events, Tear Film Osmolarity, and Discontinuations.

OBJECTIVES: To assess the relative clinical success of MiSight contact lenses (CLs) (study group) and distance single-vision (SV) spectacles (control group) in children in terms of adverse events (AEs), discontinuations, and tear film osmolarity over a 2-year period. METHODS: Seventy-four subjects aged 8 to 12 with myopia of -0.75 to -4.00 D and astigmatism less than 1.00 D were randomly assigned to MiSight CLs or SV groups. Subjects were monitored at 6-month intervals over the course of 24 months and advised to report to the clinic immediately should AEs occur. Adverse events were categorized as serious, significant, and nonsignificant. Discontinuation was defined as cessation of participation in the study. RESULTS: Forty-four children were corrected with MiSight CLs and 33 with SV spectacles. No serious or significant AEs were found in any of the participants in either group. Two nonsignificant AEs were found in MiSight group, corresponding to a foreign body on the cornea in two children. There were five discontinuations in MiSight group, one because of change of residence and four because of unwillingness to use the CL. There were no discontinuations in SV group. Neither group showed any significant changes in osmolarity data over the 24 months of follow-up (P≥0.05). CONCLUSIONS: No clinically serious events were observed in either group. Our results show that correct use of MiSight CLs is a safe option for myopia correction. The success of this treatment requires a combination of proper lens fitting, good adherence to routine follow-ups, and timely treatment of complications.

Long-Term Impacts of Orthokeratology Treatment on Sub-Basal Nerve Plexus and Corneal Sensitivity Responses and Their Reversibility.

PURPOSE: To examine the effects of one year of overnight orthokeratology (OK) treatment on the sub-basal nerve plexus (SBNP) and corneal sensitivity and to assess the reversibility of these effects one month after treatment interruption. METHODS: Thirty-two subjects with low-moderate myopia underwent OK treatment for one year. Fifteen non-contact lens wearers served as controls. At the time points baseline, one year of treatment, and one month after removing the OK lenses, two tests were conducted: corneal sensitivity (Cochet-Bonnet esthesiometer) and SBNP imaging by in vivo confocal microscopy. RESULTS: In participants wearing OK lenses, significant reductions over the year were produced in SBNP nerve density (P=0.001 and P=0.006) and number of nerves (P<0.001 and P=0.001) in the central and mid-peripheral cornea, respectively. Differences over the year were also detected in central objective tortuosity (P=0.002). After lens removal, baseline values of nerve density (P=0.024 and P=0.001) and number of nerves (P=0.021 and P<0.001) for the central and mid-peripheral cornea, respectively, were not recovered. At one month post-treatment, a difference was observed from one-year values in central corneal sensitivity (P=0.045) and mid-peripheral Langerhans cell density (P=0.033), and from baseline in mid-peripheral objective tortuosity (P=0.049). Direct correlation was detected at one year between nerve density and tortuosity both in the central (P<0.01; r=0.69) and mid-peripheral cornea (P<0.01; r=0.76). CONCLUSIONS: Long-term OK treatment led to reduced SBNP nerve density and this was directly correlated with corneal tortuosity. After one month of treatment interruption, nerve density was still reduced.

Short-Term Effects of Overnight Orthokeratology on Corneal Sub-basal Nerve Plexus Morphology and Corneal Sensitivity.

OBJECTIVE: To assess the effects of a short period of orthokeratology (OK) on corneal sub-basal nerve plexus (SBNP) morphology and corneal sensitivity. METHODS: Measurements were made in 56 right eyes of 56 subjects with low-to-moderate myopia who wore 2 OK lens designs (Group CRT: HDS 100 Paragon CRT, n=35; Group SF: Seefree; n=21) for a period of 1 month and in 15 right eyes of noncontact lens wearers as controls. The variables determined in each participant were corneal sensitivity using a Cochet-Bonnet esthesiometer and 12 SBNP variables determined on laser scanning confocal microscopy images using 3 different software packages. Correlation between SBNP architecture and corneal sensitivity was also examined. RESULTS: Few changes were observed over the 1-month period in the variables examined in the OK treatment and control groups. However, significant reductions were detected over time in the number of nerves in the central cornea in the groups CRT (P=0.029) and SF (P=0.043) and in central corneal sensitivity in CRT (P=0.047) along with significant increases in central and midperipheral corneal Langerhans cell counts in SF (P=0.001 and 0.048, respectively). CONCLUSIONS: This study provides useful data to better understand the anatomical changes induced by OK in corneal SBNP. The different response observed to the 2 OK lens designs requires further investigation.

Mooren Ulcer in a Child Wearing Orthokeratology Contact Lenses.

PURPOSE: To report a case of Mooren ulcer that developed in a pediatric patient wearing orthokeratology overnight contact lenses. METHODS: Case report. RESULTS: A 10-year-old boy was referred to our clinic because of progressive peripheral corneal ulcer in the right eye, despite the intensive use of fortified antibiotic eye drops. The patient had been using overnight orthokeratology lenses for 4 months before presentation of corneal ulcer. There was no other history of ocular or systemic trauma and disorders. Microbiological tests of the lesion were negative. Systemic evaluation showed no sign of rheumatologic disease. Under a diagnosis of Mooren ulcer, the patient was treated with topical and systemic corticosteroids. After four weeks of treatment, the patient's symptoms rapidly disappeared, and corneal ulcer was healed. The vision recovered to normal with the correction of with-the-rule astigmatism. CONCLUSIONS: Mooren ulcer can develop in pediatric patients wearing orthokeratology contact lenses. Given rapid progression of Mooren ulcer in a young population, early diagnosis and proper treatment are essential to prevent a devastating outcome.

Interaction between Corneal and Internal Ocular Aberrations Induced by Orthokeratology and Its Influential Factors.

PURPOSE: To investigate the interaction between corneal, internal, and total wavefront aberrations (WAs) and their influential factors during orthokeratology (OK) treatment in Chinese adolescents. METHODS: Thirty teenagers (n = 30 eyes) were enrolled in the study; spherical equivalent refraction (SE), corneal curvature radius (CCR), central corneal thickness (CCT), WAs, and the difference in limbal transverse diameter and OK lens diameter (ΔLLD) were detected before and after one-month OK treatment. Every component of WAs was measured simultaneously by iTrace aberrometer. The influential factors of OK-induced WAs were analyzed. RESULTS: SE and CCT decreased while CCR increased significantly (P < 0.01). Higher-order aberrations (HOAs), Spherical aberrations (SAs), and coma increased significantly (P < 0.01). Corneal horizontal coma (Z31-C) and corneal spherical aberrations (Z40-C) increased (P < 0.01). The HOAs, coma, SAs, Z31-C, Z31-T, Z40-C, and Z40-T were positively correlated with SE and CCR (P < 0.01). Z3-1-C showed negative correlations with (ΔLLD) and positive correlations with SE (P < 0.05). CONCLUSIONS: The increase in OK-induced HOAs is mainly attributed to Z31 and Z40 of cornea. Z3-1 in the internal component showed a compensative effect on the corneal vertical coma. The degree of myopic correction and increase in CCR may be the essential influential factors of the increase in Z31 and Z40. The appropriate size of the OK lens may be helpful to decrease OK-induced vertical coma.

Infectious keratitis and orthokeratology lens use: a systematic review.

PURPOSE: Myopia is a prevalent condition among Asians. Orthokeratology lens has gained popularity as a method of myopia control. This systematic review is to summarize the clinical profile of infectious keratitis in association with orthokeratology lens wear. METHODS: We searched in the PubMed and EMBASE for articles adopting the search strategy "(orthokeratology lens OR orthokeratology) AND (bacterial eye infection OR keratitis OR cornea ulcer OR microbial keratitis OR bacterial keratitis)", from the start date of the databases to August 23, 2016. Articles reporting infectious keratitis in orthokeratology lens users with data of individual cases were considered eligible for this systematic review. We recorded the outcome measures including method of diagnosis, etiological agents, duration and mode of treatment and treatment outcomes. RESULTS: Our literature search yielded 172 papers. After removing duplicated and irrelevant reports, we included 29 articles for data analysis, involving 173 eyes. Among all reported cases, the mean age at presentation was 15.4 ± 6.2 years, with a female preponderance (male-to-female ratio 1:1.7). Positive microbiological cultures were reported in 69.4% of cases, with Pseudomonas aeruginosa and Acanthamoeba being the most common etiological agents. The mean duration of hospitalization was 7.7 ± 6.7 days. Mean LogMAR visual acuity at presentation was 1.17 ± 0.78, increased to 0.33 ± 0.41 at final visit (p < 0.001). CONCLUSIONS: Despite early intervention and treatment, the majority of infections resulted in the formation of corneal scars and almost 10% of eyes needed surgical treatment. Timely awareness and treatment of keratitis should be emphasized to the users.

Predictive role of corneal Q-value differences between nasal-temporal and superior-inferior quadrants in orthokeratology lens decentration.

BACKGROUND: To investigate the association between pretreatment corneal parameters and orthokeratology lens decentration. METHODS: This retrospective study included a total of 108 eyes in 60 myopia patients, who were divided into a lens-decentration and a control group. Various pretreatment corneal parameters were analyzed by receiver operating characteristic curves (ROC curves), including corneal horizontal and vertical curvatures, diopter, corneal eccentricity (E-value), asphericity (Q-value), diameter, and astigmatism, to establish a reliable predictive model for orthokeratology lens decentration. RESULTS: The temporal and inferior quadrants are preferential sides for lens decentration, which was associated with the occurrence of complications such as ghosting and corneal epithelial staining. By further analysis, we revealed lower corneal horizontal curvature and much higher corneal Q-value differences between the nasal-temporal and superior-inferior quadrants in the lens-decentration group compared to the control group (P < 0.05). ROC curve analysis showed that the sum of Q-value differences between the nasal-temporal and superior-inferior quadrants was more sensitive than any other corneal parameters in predicting lens decentration, with an area under the curve of 0.778 and a truncation point of 0.3 (P < 0.001). CONCLUSION: The sum of pretreatment corneal Q-value differences between nasal-temporal and superior-inferior quadrants is a convenient and reliable predictor for orthokeratology lens decentration.

Conjunctival Microbiome Changes Associated With Soft Contact Lens and Orthokeratology Lens Wearing.

Purpose: Usage of different types of contact lenses is associated with increased risk of sight-threatening complications. Changes in the ocular microbiome caused by contact lens wear are suggested to affect infection development in those individuals. To address this question, this study compares conjunctival microbial communities in contact lens wearers with those in noncontact lens wearers. Methods: Paired-end sequencing of the V3 region of the 16S rRNA gene was used to characterize the bacterial communities on the conjunctival surfaces of contact lens wearers and nonwearers. Results: No differences in microbial diversity were detected between contact lens wearers and nonwearers. Nevertheless, some slight microbe variability was evident between these two different groups. Bacillus, Tatumella and Lactobacillus abundance was less in orthokeratology lens (OKL) wearers than in nonwearers. In soft contact lenses (SCL) wearers, Delftia abundance decreased whereas Elizabethkingia levels increased. The difference in the SCL and nonwearer group was smaller than that in the OKL group. Variations in the conjunctival taxonomic composition between SCL wearers were larger than those in other groups. Sex differences in the conjunctival microbiota makeup were only evident among nonwearers. Conclusions: Even though there were slight percentage changes between contact lens wearers and nonwearers in some microbes, there were no differences in their diversity. On the other hand, contact lens usage might cause relative abundance of some taxa to change. Our results will help assess whether or not conjunctival microbiome changes caused by contact lens wear affect infection risk.

Reduced Corneal Sensitivity and Sub-Basal Nerve Density in Long-Term Orthokeratology Lens Wear.

OBJECTIVES: To investigate changes in corneal sensitivity and nerve morphology in orthokeratology (OK) contact lens wear. METHODS: In a cross-sectional study, 54 subjects (aged 18-45 years) were grouped into three categories: nonlens (NL), soft lens (SCL), and OK lens wearers. Corneal sensitivity was measured at the corneal apex and 2.5 mm temporal to the apex using the Cochet-Bonnet aesthesiometer. Corneal nerve morphology was assessed by sampling a 1 mm area of the corneal sub-basal nerve plexus using the Heidelberg Retinal Tomograph with Rostock Corneal Module at the corneal apex and 2.5 mm temporal to the apex. Nerve fiber density (NFD) was calculated by measuring the total length of nerve fibers per square millimeter using Image-Pro Analyser. Comparisons between groups were made using mixed analysis of variance and post hoc paired t tests with Bonferroni correction or the Kruskal-Wallis test and post hoc Mann-Whitney U tests as appropriate. RESULTS: There was a significant difference in corneal sensitivity between the three groups (P=0.027). Central threshold was significantly higher in the OK than NL group (0.69±0.42 g/mm vs. 0.45±0.12 g/mm; P=0.048). Mid-peripheral threshold was not different between the three groups (P>0.05). There was a significant difference in NFD between the three groups (P<0.001). Central NFD was significantly less in the OK than NL and SCL groups (OK: 17.89±4.42 mm/mm, NL: 25.87±5.00 mm/mm; SCL: 24.52±4.93 mm/mm; P<0.001). Mid-peripheral NFD was not different between the three groups (P>0.05). CONCLUSIONS: Long-term OK lens wear is associated with a decrease in central corneal sensitivity and NFD. The mechanism underlying refractive change during OK treatment seems to impact both corneal sensitivity and nerve morphology.

Effect of overnight orthokeratology on conjunctival goblet cells.

OBJECTIVE: To evaluate the differences between goblet cell density (GCD) and symptomatology after one month of orthokeratology lens wear. METHODS: A pilot, short-term study was conducted. Twenty-two subjects (29.7±7.0 years old) participated voluntarily in the study. Subjects were divided into two groups: habitual silicone hydrogel contact lens wearers (SiHCLW) and new contact lens wearers (NCLW). Schirmer test, tear break up time (TBUT), Ocular Surface Disease Index (OSDI) questionnaire and conjunctival impression cytology. GCD, mucin cloud height (MCH) and cell layer thickness (CLT) were measured. All measurements were performed before orthokeratology fitting and one month after fitting to assess the evolution of the changes throughout this time. RESULTS: No differences in tear volume and TBUT between groups were found (p>0.05). However, the OSDI score was statistically better after one month of orthokeratology lens wear than the baseline for the SiHCLW group (p=0.03). Regarding the goblet cell analysis, no differences were found in CLT and MCH from the baseline visit to the one month visit for the SiHCLW compared with NCLW groups (p>0.05). At baseline, the GCD in the SiHCLW group were statistically lower than NCLW group (p<0.001). There was a significant increase in GCD after orthokeratology fitting from 121±140cell/mm(2) to 254±130cell/mm(2) (p<0.001) in the SiHCLW group. CONCLUSION: Orthokeratology improves the dry eye subject symptoms and GCD after one month of wearing in SiHCLW. These results suggest that orthokeratology could be considered a good alternative for silicone hydrogel contact lens discomfort and dryness.

The Influence of Overnight Orthokeratology on Ocular Surface and Meibomian Glands in Children and Adolescents.

PURPOSE: The aim of this study was to investigate the influence of overnight orthokeratology (OOK) on ocular surface and meibomian glands in children and adolescents. METHODS: Prospective, noncomparative study included the ocular surface disease index (OSDI), tear osmolarity, corneal and conjunctival fluorescein staining, tear film breakup time (TBUT), the Schirmer I test, and meiboscore using noncontact meibography. Immunofluorescence confocal microscopy of interleukin-1ß (IL1ß), interleukin-6 (IL6), epidermal growth factor (EGF), and matrix metalloproteinase (MMP)-9 using impression cytology filter paper was performed. The tests were performed before and at 6, 12, 24, and 36 months after OOK wear. RESULTS: Fifty-eight subjects using OOK were observed. Significant increases in OSDI score (P=0.0009) and corneal and conjunctival staining score (P<0.0001) were observed compared with baseline values at 36 and 24 months, respectively. Ocular surface and meibomian changes were noted in 2 patients (3.5%). One patient exhibited an increase in OSDI score, concurrent with a decrease in TBUT at 36 months and minor loss of the meibomian gland at the distal portion of the lower lid at 24 months. The other patients exhibited the development of papillary hypertrophy and meibomian gland distortion at 24 months. No significant changes were detected in IL1ß, IL6, EGF, or MMP expression after OOK use. CONCLUSION: Based on the findings, OOK was a relatively safe modality. However, given the potential changes in the meibomian gland and tear film stability, special attention must be paid to children with baseline meibomian gland distortions or a history of allergic conditions.

The Safety of Orthokeratology--A Systematic Review.

OBJECTIVES: The aim of this review is to evaluate the ocular safety of orthokeratology (OrthoK) treatment of myopia correction and retardation. DATA SOURCES: Clinical studies published in English and Chinese were identified from MEDLINE, EMBASE CNKI, CQVIP, and WANFANG DATA (all from 1980 to April 2015). The reference lists of the studies and the Science Citation Index were also searched. SELECTION CRITERIA: Relevant clinical studies including case series, case reports, patient/practitioner surveys, retrospective and prospective cohort studies, and clinical trials were all included in the review. The material of OrthoK lenses was limited to gas-permeable lens. MAIN RESULTS: This review incorporated a total of 170 publications, including 58 English and 112 Chinese literature. The risk of microbial keratitis in overnight OrthoK was similar to that of other overnight modality. The most common complication was corneal staining. Other clinically insignificant side effects included epithelial iron deposit, prominent fribrillary lines, and transient changes of corneal biomechanical properties. There was no long-term effect of OrthoK on corneal endothelium. CONCLUSIONS: There is sufficient evidence to suggest that OrthoK is a safe option for myopia correction and retardation. Long-term success of OrthoK treatment requires a combination of proper lens fitting, rigorous compliance to lens care regimen, good adherence to routine follow-ups, and timely treatment of complications.