[ADDITION OF LOW-CONCENTRATION ATROPINE IN COMBINATION OF DUAL-FOCUS CONTACT LENSES FOR MYOPIA CONTROL TREATMENT].

INTRODUCTION: The importance of myopia management lies in the desire to minimize the potential ocular risks that increase with high myopia. AIMS: To assess the decrease in myopia progression using topical low dose atropine combined with peripheral blur contact lenses (CL). METHODS: This retrospective review study included 25 children between the ages of 8.5 years to 14 years. The children all had a minimal increase in myopia of 0.75D during the year prior to treatment. The children were divided into two groups. The control group included 14 children who wore single-vision spectacles )SV) averaging 3.20±0.9D ranging from 1.5-5.3D. The study group included 11 children who wore dual-focus CL, with an average prescription of 3.4±0.7D ranging from 2.5 to 4.3D, for one year. At that point, when an additional myopia increase was observed, the children were additionally treated with topical 0.01% atropine for two years (CL+A0.01). RESULTS: There was an increase in myopia in the SV group of 1.12±0.52D, 1.08±0.56D and 0.96±0.53D in the first, second, and third years, respectively. The myopia increase in the CL+A0.01 group was 0.57±0.48D, 0.14±0.34D, and 0.17±0.29D in the first, second, and third years, respectively. CONCLUSIONS: Low-dose atropine combined with peripheral blur contact lenses was effective in decreasing myopia progression in this study. Additional, larger-scale studies are required in the future. DISCUSSION: This study found a significant decrease in myopia progression in the second and third years of treatment. The CL group showed less effectivity than the CL+A0.01 group.

Efficacy and Safety of 8 Atropine Concentrations for Myopia Control in Children: A Network Meta-Analysis.

TOPIC: Comparative efficacy and safety of different concentrations of atropine for myopia control. CLINICAL RELEVANCE: Atropine is known to be an effective intervention to delay myopia progression. Nonetheless, no well-supported evidence exists yet to rank the clinical outcomes of various concentrations of atropine. METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov on April 14, 2021. We selected studies involving atropine treatment of at least 1 year's duration for myopia control in children. We performed a network meta-analysis (NMA) of randomized controlled trials (RCTs) and compared 8 atropine concentrations (1% to 0.01%). We ranked the atropine concentrations for the corresponding outcomes by P score (estimate of probability of being best treatment). Our primary outcomes were mean annual changes in refraction (diopters/year) and axial length (AXL; millimeters/year). We extracted data on the proportion of eyes showing myopia progression and safety outcomes (photopic and mesopic pupil diameter, accommodation amplitude, and distance and near best-corrected visual acuity [BCVA]). RESULTS: Thirty pairwise comparisons from 16 RCTs (3272 participants) were obtained. Our NMA ranked the 1%, 0.5%, and 0.05% atropine concentrations as the 3 most beneficial for myopia control, as assessed for both primary outcomes: 1% atropine (mean differences compared with control: refraction, 0.81 [95% confidence interval (CI), 0.58-1.04]; AXL, -0.35 [-0.46 to -0.25]); 0.5% atropine (mean differences compared with control: refraction, 0.70 [95% CI, 0.40-1.00]; AXL, -0.23 [-0.38 to -0.07]); 0.05% atropine (mean differences compared with control: refraction, 0.62 [95% CI, 0.17-1.07]; AXL, -0.25 [-0.44 to -0.06]). In terms of myopia control as assessed by relative risk (RR) for overall myopia progression, 0.05% was ranked as the most beneficial concentration (RR, 0.39 [95% CI, 0.27-0.57]). The risk for adverse effects tended to rise as the atropine concentration was increased, although this tendency was not evident for distance BCVA. No valid network was formed for near BCVA. DISCUSSION: The ranking probability for efficacy was not proportional to dose (i.e., 0.05% atropine was comparable with that of high-dose atropine [1% and 0.5%]), although those for pupil size and accommodation amplitude were dose related.

Three-Year Clinical Trial of Low-Concentration Atropine for Myopia Progression (LAMP) Study: Continued Versus Washout: Phase 3 Report.

PURPOSE: (1) To compare the efficacy of continued and stopping treatment for 0.05%, 0.025%, and 0.01% atropine during the third year. (2) To evaluate the efficacy of continued treatment over 3 years. (3) To investigate the rebound phenomenon and its determinants after cessation of treatment. DESIGN: A randomized, double-masked extended trial. PARTICIPANTS: A total of 350 of 438 children aged 4 to 12 years originally recruited into the Low-Concentration Atropine for Myopia Progression (LAMP) study. METHODS: At the beginning of the third year, children in each group were randomized at a 1:1 ratio to continued treatment and washout subgroups. Cycloplegic spherical equivalent (SE) refraction and axial length (AL) were measured at 4-month intervals. MAIN OUTCOME MEASURES: Changes in SE and AL between groups. RESULTS: A total of 326 children completed 3 years of follow-up. During the third year, SE progression and AL elongation were faster in the washout subgroups than in the continued treatment groups across all concentrations: -0.68 ± 0.49 diopters (D) versus -0.28 ± 0.42 D (P < 0.001) and 0.33 ± 0.17 mm versus 0.17 ± 0.14 mm (P < 0.001) for the 0.05%; -0.57 ± 0.38 D versus -0.35 ± 0.37 D (P = 0.004) and 0.29 ± 0.14 mm versus 0.20 ± 0.15 mm (P = 0.001) for the 0.025%; -0.56 ± 0.40 D versus -0.38 ± 0.49 D (P = 0.04) and 0.29 ± 0.15 mm versus 0.24 ± 0.18 mm (P = 0.13) for the 0.01%. Over the 3-year period, SE progressions were -0.73 ± 1.04 D, -1.31 ± 0.92 D, and -1.60 ± 1.32 D (P = 0.001) for the 0.05%, 0.025%, and 0.01% groups in the continued treatment subgroups, respectively, and -1.15 ± 1.13 D, -1.47 ± 0.77 D, and -1.81 ± 1.10 D (P = 0.03), respectively, in the washout subgroup. The respective AL elongations were 0.50 ± 0.40 mm, 0.74 ± 0.41 mm, and 0.89 ± 0.53 mm (P < 0.001) for the continued treatment subgroups and 0.70 ± 0.47 mm, 0.82 ± 0.37 mm, and 0.98 ± 0.48 mm (P = 0.04) for the washout subgroup. The rebound SE progressions during washout were concentration dependent, but their differences were clinically small (P = 0.15). Older age and lower concentration were associated with smaller rebound effects in both SE progression (P < 0.001) and AL elongation (P < 0.001). CONCLUSIONS: During the third year, continued atropine treatment achieved a better effect across all concentrations compared with the washout regimen. 0.05% atropine remained the optimal concentration over 3 years in Chinese children. The differences in rebound effects were clinically small across all 3 studied atropine concentrations. Stopping treatment at an older age and lower concentration are associated with a smaller rebound.

Evolution of the Prevalence of Myopia among Taiwanese Schoolchildren: A Review of Survey Data from 1983 through 2017.

PURPOSE: The aim of this study was to evaluate the changes in the prevalence of myopia in Taiwanese schoolchildren over the past few decades and to analyze the risk factors for myopia. DESIGN: Analysis of 8 consecutive population-based myopia surveys conducted from 1983 through 2017. PARTICIPANTS: An average of 8917 (5019-11 656) schoolchildren 3 to 18 years of age were selected using stratified systematic cluster sampling or by probability proportional to size sampling. METHODS: All participants underwent complete ophthalmic evaluations. Three drops of 0.5% tropicamide were used to obtain the cycloplegic refractive status of each participant. Questionnaires were used to acquire participant data from the 1995, 2005, 2010, and 2016 surveys. MAIN OUTCOME MEASURES: Prevalence of myopia (spherical equivalence of ≤-0.25 diopter [D]) and high myopia (≤-6.0 D) was assessed. Multivariate analyses of risk factors were conducted. RESULTS: The prevalence of myopia among all age groups increased steadily. From 1983 through 2017, the weighted prevalence increased from 5.37% (95% confidence interval [CI], 3.50%-7.23%) to 25.41% (95% CI, 21.27%-29.55%) for 7-year-olds (P = 0.001 for trend) and from 30.66% (95% CI, 26.89%-34.43%) to 76.67% (95% CI, 72.94%-80.40%) for 12-year-olds (P = 0.001 for trend). The prevalence of high myopia also increased from 1.39% (95% CI, 0.43%-2.35%) to 4.26% (95% CI, 3.35%-5.17%) for 12-year-olds (P = 0.008 for trend) and from 4.37% (95% CI, 2.91%-5.82%) to 15.36% (95% CI, 13.78%-16.94%) for 15-year-olds (P = 0.039 for trend). In both the 2005 and 2016 survey samples, children who spent less than 180 minutes daily on near-work activities showed significantly lower risks for myopia developing (<60 minutes: odds ratio [OR], 0.48 and 0.56; 60-180 minutes: OR, 0.69 and 0.67). In the 2016 survey, spending more than 60 minutes daily on electronic devices was associated significantly with both myopia and high myopia (OR, 2.43 and 2.31). CONCLUSIONS: The prevalence of myopia among schoolchildren increased rapidly from 1983 through 2017 in Taiwan. The major risk factors are older age and time spent on near-work activities. Use of electronic devices increased the amount of time spent on near-work and may increase the risk of developing myopia.

Age Effect on Treatment Responses to 0.05%, 0.025%, and 0.01% Atropine: Low-Concentration Atropine for Myopia Progression Study.

PURPOSE: To investigate the effect of age at treatment and other factors on treatment response to atropine in the Low-Concentration Atropine for Myopia Progression (LAMP) Study. DESIGN: Secondary analysis from a randomized trial. PARTICIPANTS: Three hundred fifty children aged 4 to 12 years who originally were assigned to receive 0.05%, 0.025%, or 0.01% atropine or placebo once daily, and who completed 2 years of the LAMP Study, were included. In the second year, the placebo group was switched to the 0.05% atropine group. METHODS: Potential predictive factors for change in spherical equivalent (SE) and axial length (AL) over 2 years were evaluated by generalized estimating equations in each treatment group. Evaluated factors included age at treatment, gender, baseline refraction, parental myopia, time outdoors, diopter hours of near work, and treatment compliance. Estimated mean values and 95% confidence intervals (CIs) of change in SE and AL over 2 years also were generated. MAIN OUTCOME MEASURES: Factors associated with SE change and AL change over 2 years were the primary outcome measures. Associated factors during the first year were secondary outcome measures. RESULTS: In 0.05%, 0.025%, and 0.01% atropine groups, younger age was the only factor associated with SE progression (coefficient of 0.14, 0.15, and 0.20, respectively) and AL elongation (coefficient of -0.10, -0.11, and -0.12, respectively) over 2 years; the younger the age, the poorer the response. At each year of age from 4 to 12 years across the treatment groups, higher-concentration atropine showed a better treatment response, following a concentration-dependent effect (Ptrend <0.05 for each age group). In addition, the mean SE progression in 6-year-old children receiving 0.05% atropine (-0.90 diopter [D]; 95% CI, -0.99 to -0.82) was similar to that of 8-year-old children receiving 0.025% atropine (-0.89 D; 95% CI, -0.94 to -0.83) and 10-year-old children receiving 0.01% atropine (-0.92 D; 95% CI, -0.99 to -0.85). All concentrations were well tolerated in all age groups. CONCLUSIONS: Younger age is associated with poor treatment response to low-concentration atropine at 0.05%, 0.025%, and 0.01%. Among concentrations studied, younger children required the highest 0.05% concentration to achieve similar reduction in myopic progression as older children receiving lower concentrations.

Ocular surface temperature measurement in diabetic retinopathy.

Infrared thermography provides functional imaging by picturing the temperature pattern of the region imaged. The temperature correlates to the blood flow pattern and is used in the diagnosis of diseases like breast cancer, peripheral vascular disorders, diabetic neuropathy and fever screening. In the present study, the usage of ocular thermography for diagnosis of diabetic retinopathy is explored. Ocular thermograms using infrared imaging camera were obtained for normal subjects (80 volunteers - 40 males and 40 females) age groups 21-30, 31-40, 41-50 and 51-60 years, non-proliferative diabetic retinopathy (NPDR) patients (50 volunteers -25 males and 25 females) and proliferative diabetic retinopathy (PDR) patients (20 volunteers -10 males and 10 females) belonging to age group of 51-60 years. The temperature at various points of interest (POIs) and horizontal temperature profiles were studied. Ocular surface temperature (OST) and effect of eye dilation on OST was studied for control, age matched NPDR and PDR. Statistical analyses were carried out to find the significance of correlation between OST of controls and NPDR and PDR. The global minimum temperature on the ocular surface for controls (21-60 years) was found to be at cornea which is about 34.79 ± 0.68 °C, and maximum at the inner canthus viz. 36.08 ± 0.62 °C. Dilation studies showed an average increase of 0.82 ± 0.13 °C in cornea and 0.75 ± 0.14 °C in conjunctiva and limbus (p < 0.001). The temperature of cornea is around 33.22 ± 0.12 °C and 32.64 ± 0.12 °C for NPDR and PDR patients respectively, in the age group of 51-60 years. OST of NPDR patients was 0.60 ± 0.15 °C lesser than that of age matched normal eyes (p < 0.001) at cornea and limbus regions and 0.71 ± 0.20 °C at inner canthus. The OST of PDR patients was lesser than age matched controls by 1.18 ± 0.12 °C at cornea, 0.9 ± 0.13 °C at inner canthus and 1.0 ± 0.14 °C at other POIs. During dilation studies a positive variation of 0.61 ± 0.12 °C in cornea and 0.48 ± 0.13 °C in conjunctiva and limbus was observed (p < 0.001) in NPDR eyes. Similarly an average increase of 0.62 ± 0.11 °C in cornea and an average increase of 0.47 ± 0.15 °C in conjunctiva and limbus were observed (p < 0.001) in PDR eyes. The OST of NPDR and PDR patients was less compared with age matched counterparts in both pre and post dilation studies. Dilation of eye showed increase in OST for both controls and diabetic retinopathy patients. The degree of increase is less compared with controls. The variation in OST observed during pre and post dilatation studies of diabetic retinopathy patients is a functional marker of pathology, and can be used as a parameter for diagnosis.

Pharmacologic interventions for mydriasis in cataract surgery.

BACKGROUND: Cataract surgery is one of the most common surgical procedures performed worldwide. Achieving appropriate intraoperative mydriasis is one of the critical factors associated with the safety and performance of the surgery. Inadequate pupillary dilation or constriction of the pupil during cataract surgery can impair the surgeon's field of view and make it difficult to maneuver instruments. OBJECTIVES: To evaluate the relative effectiveness of achieving pupillary dilation during phacoemulsification for cataract extraction using three methods of pupillary dilation: topical mydriatics, intracameral mydriatics, or depot delivery systems. We also planned to document and compare the risk of intraoperative and postoperative complications following phacoemulsification for cataract extraction, as well as the cost-effectiveness of these methods for pupillary dilation. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 22 January 2021. SELECTION CRITERIA: We included only randomized controlled trial (RCTs) in which participants underwent phacoemulsification for cataract extraction. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: We included a total of 14 RCTs (1670 eyes of 1652 participants) in this review. Of the 14 trials, 7 compared topical versus intracameral mydriatics, 6 compared topical mydriatics versus depot delivery systems, and 1 compared all three methods. We were unable to calculate overall estimates of comparative effectiveness for most outcomes due to statistical heterogeneity among the estimates from individual studies or because outcome data were available from only a single study. Furthermore, the certainty of evidence for most outcomes was low or very low, due primarily to imprecision and risk of bias. Comparison 1: topical mydriatics versus intracameral mydriatics Four RCTs (739 participants, 757 eyes) of the 8 RCTs that had compared these two methods reported mean pupillary diameters at the time surgeons had performed capsulorhexis; all favored topical mydriatics, but heterogeneity was high (I2 = 95%). After omitting 1 RCT that used a paired-eyes design, evidence from three RCTs (721 participants and eyes) suggests that mean pupil diameter at the time of capsulorhexis may be greater with topical mydriatics than with intracameral mydriatics, but the evidence is of low certainty (mean difference 1.06 mm, 95% confidence interval (CI) 0.81 mm to 1.31 mm; I2 = 49%). Four RCTs (224 participants, 242 eyes) reported mean pupillary diameter at the beginning of cataract surgery; the effect estimates from all trials favored topical mydriatics, with very low-certainty evidence. Five RCTs (799 participants, 817 eyes) reported mean pupillary diameter at the end of cataract surgery. Data for this outcome from the largest RCT (549 participants and eyes) provided evidence of a small difference in favor of intracameral mydriasis. On the other hand, 2 small RCTs (78 participants, 96 eyes) favored topical mydriatics, and the remaining 2 RCTs (172 participants) found no meaningful difference between the two methods, with very low-certainty evidence. Five RCTs (799 participants, 817 eyes) reported total intraoperative surgical time. The largest RCT (549 participants and eyes) reported decreased total intraoperative time with intracameral mydriatics, whereas 1 RCT (18 participants, 36 eyes) favored topical mydriatics, and the remaining 3 RCTs (232 participants) found no difference between the two methods, with very low-certainty evidence. Comparison 2: topical mydriatics versus depot delivery systems Of the 7 RCTs that compared these two methods, none reported mean pupillary diameter at the time surgeons performed capsulorhexis. Six RCTs (434 participants) reported mean pupillary diameter at the beginning of cataract surgery. After omitting 1 RCT suspected to be responsible for high heterogeneity (I2 = 80%), meta-analysis of the other 5 RCTs (324 participants and eyes) found no evidence of a meaningful difference between the two methods, with very low-certainty evidence. Three RCTs (210 participants) reported mean pupillary diameter at the end of cataract surgery, with high heterogeneity among effect estimates for this outcome. Estimates of mean differences and confidence intervals from these three RCTs were consistent with no difference between the two methods. A fourth RCT reported only means for this outcome, with low-certainty evidence. Two small RCTs (118 participants) reported total intraoperative time. Surgical times were lower when depot delivery was used, but the confidence interval estimated from one trial was consistent with no difference, and only mean times were reported from the other trial, with very low-certainty evidence. Comparison 3: Intracameral mydriatics versus depot delivery systems Only one RCT (60 participants) compared intracameral mydriatics versus depot delivery system. Mean pupillary diameter at the time the surgeon performed capsulorhexis, phacoemulsification time, and cost outcomes were not reported. Mean pupil diameter at the beginning and end of cataract surgery favored the depot delivery system, with very low-certainty evidence. Adverse events Evidence from one RCT (555 participants and eyes) comparing topical mydriatics versus intracameral mydriatics suggests that ocular discomfort may be greater with topical mydriatics than with intracameral mydriatics at one week (risk ratio (RR) 10.57, 95% CI 1.37 to 81.34) and one month (RR 2.51, 95% CI 1.36 to 4.65) after cataract surgery, with moderate-certainty evidence at both time points. Another RCT (30 participants) reported iris-related complications in 11 participants in the intracameral mydriatics group versus no complications in the depot delivery system group, with very low-certainty evidence. Cardiovascular related adverse events were rarely mentioned. AUTHORS' CONCLUSIONS: Data from 14 completed RCTs were inadequate to establish the superiority of any of three methods to achieve mydriasis for cataract surgery, based on pupillary dilation at different times during the surgery or on time required for surgery. Only one trial had a sample size adequate to yield a robust effect estimate. Larger, well-designed trials are needed to provide robust estimates for the comparison of mydriasis approaches for beneficial and adverse effects.

Phentolamine Eye Drops Reverse Pharmacologically Induced Mydriasis in a Randomized Phase 2b Trial.

SIGNIFICANCE: After a dilated eye examination, many patients experience symptoms of prolonged light sensitivity, blurred vision, and cycloplegia associated with pharmacological mydriasis. Phentolamine mesylate ophthalmic solution (PMOS) may expedite the reversal of mydriasis in patients, potentially facilitating return to functional vision and reducing barriers to obtaining dilated eye examinations. PURPOSE: The protracted reversal time after pharmacologically induced pupil dilation impairs vision. We tested the hypothesis that PMOS rapidly reduces pupil diameter in this acute indication. METHODS: In this double-masked placebo-controlled, randomized, two-arm crossover phase 2b trial, we evaluated the effects of one drop of 1% PMOS applied bilaterally in subjects who had their pupils dilated by one of two common mydriatic agents: 2.5% phenylephrine or 1% tropicamide. End points included change in pupil diameter, percent of subjects returning to baseline pupil diameter, and accommodative function at multiple time points. RESULTS: Thirty-one subjects completed the study (15 dilated with phenylephrine and 16 with tropicamide). Change in pupil diameter from baseline at 2 hours after maximal dilation with 1% PMOS was -1.69 mm and was significantly greater in magnitude compared with placebo for every time point beyond 30 minutes (P < .05). At 2 hours, a greater percentage of study eyes given 1% PMOS returned to baseline pupil diameter compared with placebo (29 vs. 13%, P = .03), which was this also seen at 4 hours (P < .001). More subjects treated with PMOS in the tropicamide subgroup had at least one eye returning to baseline accommodative amplitude at 2 hours (63 vs. 38%, P = .01). There were no severe adverse events, with only mild to moderate conjunctival hyperemia that resolved in most patients by 6 hours. CONCLUSIONS: Phentolamine mesylate ophthalmic solution at 1% reversed medically induced pupil dilation more rapidly than placebo treatment regardless of which mydriatic was used (adrenergic agonists and cholinergic blockers) with a tolerable safety profile.

Adverse reactions to 1% cyclopentolate eye drops in children: an analysis using logistic regression models.

PURPOSE: To determine the frequency, symptoms and risk factors for adverse reactions to two-times instillation of 1% cyclopentolate in children. STUDY DESIGN: Prospective, observational study. METHODS: The subjects were 646 patients who underwent cycloplegic refraction with cyclopentolate (mean age; 7.0 ± 3.5 years, age range; 0-15 years). Five minutes after instillation of 0.4% oxybuprocaine hydrochloride, a 1% cyclopentolate eye drop was instilled twice, with an interval of 10 min. Fifty minutes later, two certified orthoptists evaluated adverse reactions using a questionnaire and interviewed the patients' guardians. The relationship between the adverse reaction rates and age, gender, additional instillation, complications of the central nervous system (CNS), time of day and season were analysed using binominal and polytomous logistic regression models. RESULTS: The overall frequency of adverse reactions was 18.3% (118/646 patients). The main symptoms included conjunctival injection (10.5%, 68/646), drowsiness (6.8%, 44/646) and facial flush (2.2%, 14/646). The odds ratio (OR) of conjunctival injection increased with patient's age (p < 0.05), in boys (p < 0.01) and in winter (p < 0.001). In contrast, the OR of drowsiness decreased with age (p < 0.001). Facial flush was observed mostly in children younger than 4 years. CNS complications were not a significant risk factor for any of the symptoms. CONCLUSIONS: Adverse reactions to 1% cyclopentolate eye drops were more frequent than previously expected, but all were mild and transient. The probability of each symptom was associated with a clear age-specific trend.

Is it necessary to wait several minutes between applications of different topical ophthalmic solutions? A preliminary study with tropicamide eye drops in healthy dogs.

OBJECTIVE: To evaluate the efficacy of topical tropicamide when placed at different time intervals before or after a saline drop. ANIMALS STUDIED: Eight healthy Labrador and golden retriever dogs. PROCEDURES: The effect of 1% tropicamide on pupillary diameter (PD) was measured over 240 min when administered alone (control) and then 1 and 5 min prior to, or following, application of a saline drop, with 1-week washout between each of the five trials. Data were analyzed using repeated-measures ANOVA and Tukey post hoc test. RESULTS: Only 6/110 pairwise comparisons among the 5 trials were statistically significant (p ≤ .035), with post-hoc analysis showing no significant differences (p ≥ .14) between the overall means of all trials. In all five trials, maximal PD was reached 30 min after tropicamide application and maintained until 210 min for 180 min (p = .0005). CONCLUSIONS: Our results suggest that waiting 1 min between applications of different ophthalmic solutions may be sufficient for maximal drug effect. Care should be taken when extrapolating these results to other species and different ophthalmic formulations.

Accuracy of Autorefraction in Children: A Report by the American Academy of Ophthalmology.

PURPOSE: The purpose of this assessment is to evaluate the accuracy of autorefraction compared with cycloplegic retinoscopy in children. METHODS: Literature searches were last conducted in October 2019 in the PubMed and the Cochrane Library databases for studies published in English. The combined searches yielded 118 citations, of which 53 were reviewed in full text. Of these, 31 articles were deemed appropriate for inclusion in this assessment and subsequently assigned a level of evidence rating by the panel methodologists. Four articles were rated level I, 11 were rated level II, and 16 were rated level III articles. The 16 level III articles were excluded from this review. RESULTS: Thirteen of the 15 studies comparing cycloplegic autorefraction with cycloplegic retinoscopy found a mean difference in spherical equivalent or sphere of less than 0.5 diopters (D); most were less than 0.25 D. Even lower mean differences were found when evaluating the cylindrical component of cycloplegic autorefraction versus cycloplegic retinoscopy. Despite low mean variability, there was significant individual measurement variability; the 95% limits of agreement were wide and included clinically relevant differences. Comparisons of noncycloplegic with cycloplegic autorefractions found that noncyloplegic refraction tends to over minus by 1 to 2 D. CONCLUSIONS: Cycloplegic autorefraction is appropriate to use in pediatric population-based studies. Cycloplegic retinoscopy can be valuable in individual clinical cases to confirm the accuracy of cycloplegic autorefraction, particularly when corrected visual acuity is worse than expected or the autorefraction results are not consistent with expected findings.

Differential Effects on Ocular Biometrics by 0.05%, 0.025%, and 0.01% Atropine: Low-Concentration Atropine for Myopia Progression Study.

PURPOSE: To evaluate changes in ocular biometrics in groups receiving 0.05%, 0.025%, and 0.01% atropine compared with placebo over 1 year based on the Low-Concentration Atropine for Myopia Progression (LAMP) study. DESIGN: Double-blinded, randomized, placebo-controlled trial. PARTICIPANTS: Three hundred eighty-three children aged 4 to 12 years who were assigned randomly to receive 0.05%, 0.025%, 0.01% atropine, or placebo once daily in both eyes and completed the first year of the LAMP study. METHODS: Cycloplegic spherical equivalent (SE), axial length (AL), corneal curvature (K), and anterior chamber depth (ACD) were measured by IOLMaster. Corneal astigmatism and lens power were calculated. The ocular biometric parameter changes were compared among groups. Contributions to SE progression from ocular parameters were determined and compared among groups. MAIN OUTCOME MEASURES: Changes in ocular biometrics and their associations with the changes in SE. RESULTS: Over 1 year, changes in AL were 0.20 ± 0.25 mm, 0.29 ± 0.20 mm, 0.36 ± 0.29 mm, and 0.41 ± 0.22 mm in the 0.05% atropine, 0.025% atropine, 0.01% atropine, and placebo groups, respectively (P < 0.001), with a concentration-dependent response. Corneal power remained stable, and its changes were similar across all atropine concentrations: -0.02 ± 0.14 diopter (D), -0.01 ± 0.14 D, -0.01 ± 0.12 D, and 0.01 ± 0.14 D in the 0.05% atropine, 0.025% atropine, 0.01% atropine, and placebo groups, respectively (P = 0.10). Lens power decreased over time in each concentration, but its changes also were similar across all concentrations: -0.31 ± 0.43 D, -0.38 ± 0.47 D, -0.40 ± 0.43 D, and -0.41 ± 0.43 D in the 0.05% atropine, 0.025% atropine, 0.01% atropine, and placebo groups, respectively (P = 0.24). Changes in ACD remained similar across all concentrations (P = 0.41). The contributions to SE progression from the ocular biometric changes after adjusting for age and gender in each concentration were similar across all groups (P > 0.05). CONCLUSIONS: Low-concentrations of atropine (0.05%, 0.025%, and 0.01%) have no clinical effect on corneal or lens power. Antimyopic effects of low-concentration atropine act mainly on reducing AL elongation, and therefore could reduce the risk of subsequent myopia complications.

Two-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression (LAMP) Study: Phase 2 Report.

PURPOSE: To evaluate the efficacy and safety of 0.05%, 0.025%, and 0.01% atropine eye drops over 2 years to determine which is the optimal concentration for longer-term myopia control. DESIGN: Randomized, double-masked trial extended from the Low-Concentration Atropine for Myopia Progression (LAMP) Study. PARTICIPANTS: Three hundred eighty-three of 438 children (87%) aged 4 to 12 years with myopia of at least -1.0 diopter (D) originally randomized to receive atropine 0.05%, 0.025%, 0.01%, or placebo once daily in both eyes in the LAMP phase 1 study were continued in this extended trial (phase 2). METHODS: Children in the placebo group (phase 1) were switched to receive 0.05% atropine from the beginning of the second-year follow-up, whereas those in the 0.05%, 0.025%, and 0.01% atropine groups continued with the same regimen. Cycloplegic refraction, axial length (AL), accommodation amplitude, photopic and mesopic pupil diameter, and best-corrected visual acuity were measured at 4-month intervals. MAIN OUTCOME MEASURES: Changes in spherical equivalent (SE) and AL and their differences between groups. RESULTS: Over the 2-year period, the mean SE progression was 0.55±0.86 D, 0.85±0.73 D, and 1.12±0.85 D in the 0.05%, 0.025%, and 0.01% atropine groups, respectively (P = 0.015, P < 0.001, and P = 0.02, respectively, for pairwise comparisons), with mean AL changes over 2 years of 0.39±0.35 mm, 0.50±0.33 mm, and 0.59±0.38 mm (P = 0.04, P < 0.001, and P = 0.10, respectively). Compared with the first year, the second-year efficacy of 0.05% and 0.025% atropine remained similar (P >0.1), but improved mildly in the 0.01% atropine group (P = 0.04). For the phase 1 placebo group, the myopia progression was reduced significantly after switching to 0.05% atropine (SE change, 0.18 D in second year vs. 0.82 D in first year [P < 0.001]; AL elongated 0.15 mm in second year vs. 0.43 mm in first year [P < 0.001]). Accommodation loss and change in pupil size in all concentrations remained similar to the first-year results and were well tolerated. Visual acuity and vision-related quality of life remained unaffected. CONCLUSIONS: Over 2 years, the efficacy of 0.05% atropine observed was double that observed with 0.01% atropine, and it remained the optimal concentration among the studied atropine concentrations in slowing myopia progression.

Screening for diabetic retinopathy in diabetic patients with a mydriasis-free, full-field flicker electroretinogram recording device.

PURPOSE: To investigate the accuracy of the RETeval full-field flicker ERG in the screening of diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) and to determine a suitable range of DR diagnostic reference for patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study involving 172 subjects with T2DM, including 71 subjects without clinically detectable DR (NDR), 25 subjects with mild non-proliferative diabetic retinopathy (NPDR), 24 subjects with moderate NPDR, 27 subjects with severe NPDR and 25 subjects with proliferative diabetic retinopathy (PDR). All the subjects underwent a full-field flicker ERG using the RETeval device (DR assessment protocol), which is a mydriasis-free, full-field electroretinogram (ERG) recording system. The performance of the DR assessment protocol in detecting the DR (including mild NPDR, moderate NPDR, severe NPDR and PDR) and VTDR was analyzed with the receiver operating characteristic (ROC) curve. RESULTS: For the detection of DR (mild NPDR, moderate NPDR, severe NPDR, PDR), the area under the ROC curve was 0.867 (p < 0.001, 95% CI 0.814-0.920), and the best cutoff value for DR was determined to be 20.75, with a sensitivity of 80.2% and specificity of 81.7%. Meanwhile, for the detection of VTDR, the area under the ROC curve was 0.965 (p < 0.001, 95% CI 0.941-0.989), and the best cutoff value was set to 23.05, with a sensitivity of 94.6% and a specificity of 88.8%. CONCLUSION: The DR assessment protocol in RETeval device was effective in screening for DR (mild NPDR, moderate NPDR, severe NPDR, PDR) and VTDR in patients with diabetes. It could be helpful in referring and managing patients with T2DM in primary healthcare setting. However, caution should be taken that optimal cutoff value of DR assessment protocol may vary in different ethnic populations.

Stopping the rise of myopia in Asia.

This review discusses the rapid rise of myopia among school-age children in East and Southeast Asia during the last 60 years. It describes the history, epidemiology, and presumed causes of myopia in Asia, but also in Europe and the United States. The recent myopia boom is attributed primarily to the educational pressure in Asian countries, which prompts children to read for long hours, often under poor lighting and on computer screens. This practice severely limits the time spent outdoors and reduces exposure to sunlight and far vision. As a consequence, the eyes grow longer and become myopic. In a breakthrough study in Taiwan, it has been found that by increasing the time spent outdoors, the incidence of new myopia cases was reduced to half when children were sent onto the schoolyard for at least 2 h daily. This protection is attributed to the light-induced retinal dopamine, which blocks the abnormal growth of the eyeball. Once myopia has set in, low-dose atropine and orthokeratology have shown positive results in slowing myopia progression. Also, prismatic bifocal lenses and specially designed multifocal soft contact lenses have recently been tested with promising results. Treatment, however, must be initiated early as the disease progresses once it has started, thereby enhancing the risk for severe visual impairment and ultimately blindness.

Studies on retinal mechanisms possibly related to myopia inhibition by atropine in the chicken.

PURPOSE: While low-dose atropine eye drops are currently widely used to inhibit myopia development in children, the underlying mechanisms are poorly understood. Therefore, we studied possible retinal mechanisms and receptors that are potentially involved in myopia inhibition by atropine. METHODS: A total of 250 µg atropine were intravitreally injected into one eye of 19 chickens, while the fellow eyes received saline and served as controls. After 1 h, 1.5 h, 2 h, 3 h, and 4 h, eyes were prepared for vitreal dopamine (DA) measurements, using high-pressure liquid chromatography with electrochemical detection. Twenty-four animals were kept either in bright light (8500 lx) or standard light (500 lx) after atropine injection for 1.5 h before DA was measured. In 10 chickens, the α2A-adrenoreceptor (α2A-ADR) agonists brimonidine and clonidine were intravitreally injected into one eye, the fellow eye served as control, and vitreal DA content was measured after 1.5 h. In 6 chickens, immunohistochemical analyses were performed 1.5 h after atropine injection. RESULTS: Vitreal DA levels increased after a single intravitreal atropine injection, with a peak difference between both eyes after 1.97 h. DA was also enhanced in fellow eyes, suggesting a systemic action of intravitreally administered atropine. Bright light and atropine (which both inhibit myopia) had additive effects on DA release. Quantitative immunolabelling showed that atropine heavily stimulated retinal activity markers ZENK and c-Fos in cells of the inner nuclear layer. Since atropine was recently found to also bind to α2A-ADRs at doses where it can inhibit myopia, their retinal localization was studied. In amacrine cells, α2A-ADRs were colocalized with tyrosine hydroxylase (TH), glucagon, and nitric oxide synthase, peptides known to play a role in myopia development in chickens. Intravitreal atropine injection reduced the number of neurons that were double-labelled for TH and α2A-ADR. α2A-ADR agonists clonidine and brimonidine (which were also found by other authors to inhibit myopia) severely reduced vitreal DA content in both injected and fellow eyes, compared to eyes of untreated chicks. CONCLUSIONS: Merging our results with published data, it can be concluded that both muscarinic and α2A-adrenergic receptors are expressed on dopaminergic neurons and both atropine and α2A-ADR antagonists stimulate DA release whereas α2A-ADR agonists strongly suppress its release. Stimulation of DA by atropine was enhanced by bright light. Results are in line with the hypothesis that inhibition of deprivation myopia is correlated with DA stimulation, as long as no toxicity is involved.

Recovery dynamics of multifocal pupillographic objective perimetry from tropicamide dilation.

PURPOSE: To study the pupillary system by combining mydriasis and multifocal pupillographic objective perimetry (mfPOP). In particular, we explored how the dynamics of recovery differ for concurrently measured direct and consensual sensitivity, response delay, and signal-to-noise ratios (SNRs) for binocular mydriasis. METHODS: We recruited 26 normal participants, all with brown irides. The dichoptic mfPOP stimuli concurrently assessed 44-region/eye and both pupils. Two pre-dilation tests were followed by pairs of repeated tests at 1, 2, 4, 6, 8, 12, 24, and 48 h following dilation of both pupils with 1% tropicamide. Three subjects were retested with only the right pupil dilated. Linear models determined the independent effects of mydriasis upon the per-region and pupil measures over time. RESULTS: Post-dilation, the per-region delays initially decreased by 16.3 ± 6.02 ms (mean ± SE) (p < 0.0001, cf. baseline of 471.1 ± 4.36 ms), then increased to slower than baseline by 17.42 ± 5.57 ms after 4 h (p < 0.002), recovering to baseline at 8 h. By comparison, per-region sensitivities (constriction amplitudes) were still reduced by - 6.20 ± 0.70 µm at 8 h (p < 0.0001, cf. baseline of 21.1 ± 0.55 µm), recovered at 24 h, but rebounded at 48 h (p = 0.005). The SNRs for sensitivities and delays both recovered by 8-12 h. Across all the data, sensitivities reduced by 2.67 ± 0.25 µm/decade of age, and delay increased by 15.4 ± 1.98 ms/decade (both p < 0.00001). Data from 3 of the 26 subjects who repeated the testing for monocular dilation found that consensual response sensitivities were larger than direct for 8 h (p < 0.018). CONCLUSIONS: The per-region sensitivities were affected for longer than SNRs or delays. Strong early SNRs indicated proportionately lower pupil noise for larger pupil diameters. Following mydriasis with tropicamide 1%, the constriction amplitude measurements with mfPOP should be considered only after 48 h, but time-to-peak can be measured after 8-12 h.

Safety and efficacy of a standardized intracameral combination of mydriatics and anesthetic for cataract surgery in type-2 diabetic patients.

BACKGROUND: Cataract surgery in diabetics is more technically challenging due to a number of factors including poor intraoperative pupil dilation and a higher risk of vision threatening complications. This study evaluates the safety and efficacy of an intracameral combination of 2 mydriatics and 1 anesthetic (ICMA, Mydrane) for cataract surgery in patients with well-controlled type-2 diabetes. METHODS: Post-hoc subgroup analysis of a phase 3 randomized study, comparing ICMA to a conventional topical regimen. Data were collected from 68 centers in Europe and Algeria. Only well-controlled type-2 diabetics, free of pre-proliferative retinopathy, were included. The results for non-diabetics are also reported. The primary efficacy variable was successful capsulorhexis without additional mydriatic treatment. Postoperative safety included adverse events, endothelial cell density and vision. RESULTS: Among 591 randomized patients, 57 (9.6%) had controlled type 2 diabetes [24 (42.1%) in the ICMA Group and 33 (57.9%) in the Topical Group; intention-to-treat (ITT) set]. Among diabetics, capsulorhexis was successfully performed without additional mydriatics in 24 (96.0%; modified-ITT set) patients in the ICMA Group and 26 (89.7%) in the Topical Group. These proportions were similar in non-diabetics. No diabetic patient [1 (0.5%) non-diabetics] in the ICMA Group had a significant decrease in pupil size (≥3 mm) intraoperatively compared to 4 (16.0%; modified-ITT set) diabetics [16 (7.3%) non-diabetics] in the Topical group. Ocular AE among diabetics occurred in 2 (8.0%; Safety set) patients in the ICMA Group and 5 (16.7%) in the Topical Group. Endothelial cell density at 1 month postoperatively was similar between groups in diabetics (P = 0.627) and non-diabetics (P = 0.368). CONCLUSIONS: ICMA is effective and can be safely used in patients with well-controlled diabetes, with potential advantages compared to a topical regimen including reduced systemic risk, better corneal integrity and reduced risk of ocular complications. TRIAL REGISTRATION: The trial was registered at (reference # NCT02101359) on April 2, 2014.

The Effect of Cyclopentolate on Ocular Biometric Components.

SIGNIFICANCE: It is apparent that a variety of biometric changes are caused by different types of cycloplegic eye drops. However, these effects are inconsistent and have not been reported in different refractive groups. PURPOSE: The purpose of this study was to determine the effect of cyclopentolate 1% on ocular biometric components in different types of refractive errors in children. METHODS: This cross-sectional study was conducted on 226 eyes of 113 schoolchildren in Shahroud, northeast Iran, with a mean ± standard deviation age of 9.20 ± 1.65 years. All participants had noncycloplegic and cycloplegic objective refraction using an autorefractometer. Cycloplegia was induced using cyclopentolate 1% eye drops. Biometric measurements were made with Allegro Biograph (WaveLight AG, Erlangen, Germany) before and after administering cycloplegic drops. Mixed-effect model regression was used to analyze the data. RESULTS: After cycloplegia, the vitreous chamber depth (VCD) (-0.043; 95% confidence interval [CI], -0.067 to -0.019 mm), lens thickness (-0.146; 95% CI, -0.175 to -0.117 mm), axial length (-0.009; 95% CI, -0.012 to -0.006 mm), and lens power (-0.335; 95% CI, -0.463 to -0.208 D) decreased significantly, whereas the anterior chamber depth (ACD) (0.183; 95% CI, 0.164 to 0.202 mm), anterior segment length (0.036; 95% CI, 0.014 to 0.058) mm), lens central point (0.109; 95% CI, 0.094 to 0.124 mm), and pupil diameter (1.599; 95% CI, 1.482 to 1.716 mm) increased (P value for all tests, <.001). For changes in VCD and ACD, a significant interaction was observed between different types of refractive errors and cycloplegia, such that the adjusted mean change for ACD was significantly lower and for VCD was significantly higher in hyperopes compared with emmetropes. Lens center moves backward in myopes (0.17 mm) and stays the same in hyperopes under cycloplegia. CONCLUSIONS: According to the findings of this study, cycloplegia reduces the thickness of the crystalline lens and subsequently causes an increase in the ACD. Cycloplegia-related ocular biometric changes were different by type of refractive error.

Repeatability and Validity of Peripheral Refraction with Two Different Autorefractors.

SIGNIFICANCE: The Welch Allyn SureSight (Welch Allyn, Skaneateles Falls, NY) and Plusoptix PowerRefractor (Plusoptix, Nuremberg, Germany) are often used with infants, but little is known about the repeatability and validity of their peripheral refractive error measurements. Selecting the best instrument will support future refractive error and emmetropization studies. PURPOSE: The purpose of this study was to determine the validity and repeatability of peripheral refractive error measurements and peripheral refraction profiles measured with the Welch Allyn SureSight and Plusoptix PowerRefractor compared with the criterion standard Grand Seiko WR-5100K (Grand Seiko Co., Hiroshima, Japan). METHODS: Cycloplegic (tropicamide 1%) autorefraction was measured in the right eyes of 21 adult subjects (31.4 ± 10.4 years) with the three instruments in randomized order on two separate visits, at least 24 hours apart, centrally, and at 30 and 20° temporal and nasal gaze. RESULTS: The SureSight measurements were within 0.24 D and not significantly different from the Grand Seiko WR-5100K in any gaze (P < .65), whereas the PowerRefractor measurements were more myopic by as much as -0.97 D and significantly different in four of the five gaze directions (P < .04). The 95% limits of agreement between occasions by gaze ranged from ±0.38 to ±0.61 D for the SureSight, similar to or slightly better than the WR-5100K (±0.31 to ±1.51 D) and the PowerRefractor (±0.72 to ±1.71 D). There were no significant differences between visits for any instrument in any gaze (P < .94). The repeatability of the SureSight was also better than that for the Grand Seiko when peripheral refraction was represented by quadratic fits to the data. CONCLUSIONS: These findings suggest that the Welch Allyn SureSight is the most suitable portable autorefractor to use to monitor peripheral autorefraction based on better repeatability between occasions and better validity compared with the criterion standard Grand Seiko WR-5100K.