[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.

Changes in ocular biometrics following cycloplegic refraction in strabismic and amblyopic children.

This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to measure refractive error accurately by paralyzing accommodation. However, effects on axial length (AL), anterior chamber depth (ACD), keratometry (Km), and white-to-white distance (WTW) are not well studied in this population. This retrospective study examined 797 patients (1566 eyes) undergoing cycloplegic refraction at a Samsung Kangbuk hospital pediatric ophthalmology clinic from 2010 to 2023. Ocular biometry was measured before and after instilling 1% cyclopentolate and 0.5% phenylephrine/0.5% tropicamide. Patients were categorized by strabismus diagnosis, age, refractive error and amblyopia status. Differences in AL, ACD, Km, WTW, and refractive error pre- and post-cycloplegia were analyzed using paired t tests. ACD (3.44 ±â€…0.33 vs 3.58 ±â€…0.29 mm, P < .05) and WTW (12.09 ±â€…0.42 vs 12.30 ±â€…0.60 mm, P < .05) increased significantly after cycloplegia in all groups except other strabismus subgroup (Cs) in both parameters and youngest subgroup (G1) in ACD. Refractive error demonstrated a hyperopic shift from -0.48 ±â€…3.00 D to -0.06 ±â€…3.32 D (P < .05) in overall and a myopic shift from -6.97 ±â€…4.27 to -8.10 ±â€…2.26 in high myopia (HM). Also, AL and Km did not change significantly. In conclusion, cycloplegia impacts ocular biometrics in children with strabismus and amblyopia, significantly increasing ACD and WTW. Refractive error shifts hyperopically in esotropia subgroup (ET) and myopically in high myopia subgroup (HM), eldest subgroup (G3) relating more to anterior segment changes than AL/Km. Understanding cycloplegic effects on biometry is important for optimizing refractive correction in these patients.

Comparison of Spot Vision Screener and Tabletop Autorefractometer with Retinoscopy in the Pediatric Population.

Objectives: Determining the accuracy of cycloplegic refractive error measurements made with the Spot Vision Screener (SVS, Welch Allyn Inc, Skaneateles Falls, NY, USA) is important for refractive assessment of uncooperative patients during optometric examinations. This study compared cycloplegic refractive errors measured by SVS and tabletop autorefractometer to cycloplegic retinoscopy in children. Materials and Methods: Eighty-eight eyes of 44 subjects were examined in the study. Refractive error measurements were obtained under cycloplegia using retinoscopy, SVS, and Nidek ARK-530 tabletop autorefractometer (ARK-530, Nidek, Japan). Spherical and cylindrical values, spherical equivalents (SE), and Jackson cross-cylinder values at axes of 0° (J0) and 45° (J45) were recorded. Correlations between methods were analyzed using intraclass correlation coefficient (ICC) and Bland-Altman analysis. Results: The mean age was 7 years (range: 6 months-17 years). Sixteen (36%) of the subjects were female and 28 (64%) were male. For SE there was excellent agreement between retinoscopy and SVS (ICC: 0.924) and between retinoscopy and tabletop autorefractometer (ICC: 0.995). While there was a moderate correlation between retinoscopy and SVS for cylindrical values (ICC: 0.686), excellent correlation was detected between retinoscopy and autorefractometer (ICC: 0.966). J0 and J45 crosscylinder power values were not correlated between retinoscopy and SVS (ICC: 0.472) or retinoscopy and tabletop autorefractometer (ICC: 0.442). Retinoscopy was correlated with both SVS and tabletop autorefractometer for all parameters within ±1.96 standard deviations in Bland-Altman analysis. Conclusion: Cycloplegic retinoscopy is the gold standard for refractive error measurement in the pediatric population. However, it requires time and experienced professionals. This study revealed moderate to good agreement between SVS and retinoscopy, with better agreement in spherical errors than cylindrical errors. Although the SVS is intended for screening programs, it may also be useful in the pediatric eye office to estimate spherical refractive error in uncooperative patients.

Comparisons of handheld retinal imaging devices with ultrawide field images for determining diabetic retinopathy severity.

PURPOSE: To compare diabetic retinopathy (DR) severity identified on handheld retinal imaging with ultrawide field (UWF) images. METHODS: Mydriatic images of 225 eyes of 118 diabetic patients were prospectively imaged with the Aurora (AU) handheld retinal camera [5-field protocol (macula-centred, disc-centred, temporal, superior, inferior)] and compared with UWF images. Images were classified based on the international classification for DR. Sensitivity, specificity, kappa statistics (K/Kw) were calculated on an eye and person-level. RESULTS: Distribution of DR severity by AU/UWF images (%) by eye was no DR 41.3/36.0, mild non-proliferative DR (NPDR) 18.7/17.8, moderate 10.2/10.7, severe 16.4/15.1, proliferative DR (PDR) 13.3/20.4. Agreement between UWF and AU was exact in 64.4%, within 1-step 90.7%, k = 0.55 (95% CI:0.45-0.65), and kw = 0.79 (95% CI:0.73-0.85) by eye, and exact in 68%, within 1-step 92.9%, k = 0.58 (95% CI:0.50-0.66), and kw = 0.76 (95% CI:0.70-0.81) by person. Sensitivity/specificity for any DR, refDR, vtDR and PDR were as follows: 0.90/0.83, 0.90/0.97, 0.82/0.95 and 0.69/1.00 by person and 0.86/0.90, 0.84/0.98, 0.75/0.95 and 0.63/0.99 by eye. Handheld imaging missed 37% (17/46) eyes and 30.8% (8/26) persons with PDR. Only 3.9% (1/26) persons or 6.5% (3/46) eyes with PDR were missed if a referral threshold of moderate NPDR was used. CONCLUSIONS: Data from this study show that comparing UWF and handheld images, when PDR was the referral threshold for handheld devices, 37.0% of eyes or 30.8% of patients with PDR were missed. Due to the identification of neovascular lesions outside of the handheld fields, lower referral thresholds are needed if handheld devices are used.

Comparison of cycloplegia at 20- and 30-minutes following proxymetacaine and cyclopentolate instillation in white 12-13-year-olds.

CLINICAL RELEVANCE: Reducing the time between drop instillation and refraction reduces the time paediatric patients and young adults spend in practice, facilitating more eye examinations daily. BACKGROUND: The current procedure for paediatric cycloplegic refraction is to wait for at least 30-minutes post-instillation of a cycloplegic before measuring spherical equivalent refraction. This study compared cycloplegia at 20- and 30-minutes following 0.5% proxymetacaine and 1.0% cyclopentolate in 12-13-year-olds. METHODS: Participants were 99 white 12-13-year-olds. One drop of proxymetacaine hydrochloride (Minims, 0.5% w/v, Bausch & Lomb, UK) followed by one drop of cyclopentolate hydrochloride (Minims, 1.0% w/v, Bausch & Lomb, UK) was instilled into both eyes. Spherical equivalent refraction was measured by autorefraction (Dong Yang Rekto ORK-11 Auto Ref-Keratometer) at 20- and 30-minutes post-instillation. Data were analysed through paired t-testing, correlations, and linear regression analysis. RESULTS: There was no significant difference in level of cycloplegia achieved at 20- (Mean spherical equivalent refraction (standard deviation) 0.438 (1.404) D) and 30-minutes (0.487 (1.420) D) post-eyedrop instillation (t (98) = 1.667, p = 0.099). The mean spherical equivalent refraction difference between time points was small (0.049 (0.294) D, 95% confidence interval =-0.108 ̶ 0.009D). Agreement indices: Accuracy = 0.999, Precision = 0.973, Concordance = 0.972. Spherical equivalent refraction at 20- and 30-minutes differed by ≤0.50D in 92% of eyes, and by <1.00D in 95%. CONCLUSIONS: There was no clinically significant difference in spherical equivalent refraction or level of cycloplegia at 20- and 30-minutes post-eyedrop instillation. The latent time between drop instillation and measurement of refractive error may be reduced to 20 minutes in White 12-13-year-olds and young adults. Further studies must determine if these results persist in younger children and non-White populations.

A hydrophilic interaction liquid chromatography - Tandem mass spectrometry method for the determination of phenylephrine in dried blood spots from preterm infants.

A sensitive and accurate hydrophilic interaction liquid chromatography - tandem mass spectrometry method (HILIC-MS/MS) was developed and validated for the determination of phenylephrine concentration in Dried Blood Spot (DBS) samples from preterm infants, after ocular administration of an ophthalmic solution with phenylephrine. Sample preparation involved the extraction of the analyte from an 85 µL DBS sample with methanol - acetonitrile (50:50, v/v). Chromatographic separation was achieved on an ACQUITY UPLC BEH AMIDE column, under isocratic conditions within a 5 min run. Detection was achieved with a triple quadrupole MS applying electrospray ionization in positive mode. The method was fully validated and proved precise and accurate with in a linear range of 0.59-3.53 ng/ml in blood. The method was developed to provide insights on the level of exposure of infant population to phenylephrine after ocular administration.

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.

Safety and efficacy of 0.02% and 0.01% atropine on controlling myopia progression: a 2-year clinical trial.

Four hundred myopic children randomly received atropine 0.02% (n = 138) or 0.01% (n = 142) in both eyes once-nightly or only wore single-vision spectacles (control group) (n = 120) for 2 years. Spherical equivalent refractive error (SER), axial length (AL), pupil diameter (PD), and amplitude of accommodation (AMP) were measured every 4 months. After 2 years, the SER changes were - 0.80 (0.52) D, - 0.93 (0.59) D and - 1.33 (0.72) D and the AL changes were 0.62 (0.29) mm, 0.72 (0.31) mm and 0.88 (0.35) mm in the 0.02% and 0.01% atropine groups and control group, respectively. There were significant differences between changes in SER and AL in the three groups (all P < 0.001). The changes in SER and AL in the 2nd year were similar to the changes in the 1st year in the three groups (all P > 0.05). From baseline to 2 years, the overall decrease in AMP and increase in PD were not significantly different in the two atropine groups, whereas the AMP and PD in the control group remained stable (all P > 0.05). 0.02% atropine had a better effect on myopia control than 0.01% atropine, and its effects on PD and AMP were similar to 0.01% atropine. 0.02% or 0.01% atropine controlled myopia progression and AL elongation synchronously and had similar effects on myopia control each year.

A multicenter Spanish study of atropine 0.01% in childhood myopia progression.

To evaluate the efficacy and safety of atropine 0.01% eye drops for myopia control in a multicentric pediatric Spanish cohort. An interventional, prospective, multicenter study was designed. Children aged between 6 and 14 years, with myopia between - 2.00 D to - 6.00 D, astigmatism < 1.50 D and documented previous annual progression greater than - 0.5 D (cycloplegic spherical equivalent, SE) were included. Once nightly atropine 0.01% eye drops in each eye were prescribed to all participants for 12 months. Age, gender, ethnicity and iris color were registered. All patients underwent the same follow-up protocol in every center: baseline visit, telephone consultation 2 weeks later and office controls at 4, 8 and 12 months. At each visit, best-corrected visual acuity, and cycloplegic autorefraction were assessed. Axial length (AL), anterior chamber depth and pupil diameter were measured on an IOL Master (Carl Zeiss Meditec, Inc, Dublin, CA). Adverse effects were registered in a specific questionnaire. Mean changes in cycloplegic SE and AL in the 12 months follow-up were analyzed. SE progression during treatment was compared with the SE progression in the year before enrollment for each patient. Correlation between SE and AL, and annual progression distribution were evaluated. Progression risk factors were analyzed by multivariate logistic regression analyses. Of the 105 recruited children, 92 completed the treatment. Mean SE and AL changes were - 0.44 ± 0.41 D and 0.27 ± 0.20 mm respectively. Mean SE progression was lower than the year before treatment (- 0.44 ± 0.41 D versus - 1.01 ± 0.38 D; p < 0.0001). An inverse correlation between SE progression and AL progression (r: - 0.42; p < 0.0001) was found. Fifty-seven patients (62%) had a SE progression less than - 0.50 D. No risk factors associated with progression could be identified in multivariate analyses. Mean pupil diameter increment at 12-months visit was 0.74 ± 1.76 mm. The adverse effects were mild and infrequent, and decreased over the time. Atropine 0.01% is effective and safe for myopia progression control in a multicentric Spanish children cohort. We believe this efficacy might be extensible to the myopic pediatric population from Western countries with similar social and demographic features. More studies about myopia progression risk factors among atropine treated patients are needed.

Systemic adverse events after screening of retinopathy of prematurity with mydriatic.

PURPOSE: To evaluate systemic adverse events after screening for retinopathy of prematurity (ROP) performed with mydriatic. METHODS: This was a retrospective case series study. Medical records of consecutive patients who underwent screening for ROP with 0.5% phenylephrine and 0.5% tropicamide eyedrops were retrospectively reviewed. The score of abdominal distention (0-5), volume of milk sucked and volume of stool, along with systemic details (pulse and respiration rates, blood pressure and number of periods of apnea) were collected at 1 week and 1 day before ROP examination, and at 1 day after examination. Results were compared between the days before and after examination. Correlation between body weight at the time of examination and the score of abdominal distention was examined. The numbers of infants with abdominal and/or systemic adverse events were compared between pre- and post-examination periods. RESULTS: Eighty-six infants met the inclusion criteria. The score of abdominal distention increased from 2.0 at 1 day before examination to 2.3 at 1 day after examination (p = 0.005), and the number of infants who had worsened abdominal distension increased after examination (p = 0.01). Infants with lower body weight had a higher score of abdominal distention (p < 0.0001, r = -0.57). The number of infants with reduced milk consumption increased after examination (p = 0.0001), as did the number of infants with decreased pulse rate (p = 0.0008). CONCLUSIONS: Screening for ROP with mydriatic may have adverse effects on systemic conditions. Infants should be carefully monitored after ROP screening with mydriatic.

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.

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.

Deep learning for gradability classification of handheld, non-mydriatic retinal images.

Screening effectively identifies patients at risk of sight-threatening diabetic retinopathy (STDR) when retinal images are captured through dilated pupils. Pharmacological mydriasis is not logistically feasible in non-clinical, community DR screening, where acquiring gradable retinal images using handheld devices exhibits high technical failure rates, reducing STDR detection. Deep learning (DL) based gradability predictions at acquisition could prompt device operators to recapture insufficient quality images, increasing gradable image proportions and consequently STDR detection. Non-mydriatic retinal images were captured as part of SMART India, a cross-sectional, multi-site, community-based, house-to-house DR screening study between August 2018 and December 2019 using the Zeiss Visuscout 100 handheld camera. From 18,277 patient eyes (40,126 images), 16,170 patient eyes (35,319 images) were eligible and 3261 retinal images (1490 patient eyes) were sampled then labelled by two ophthalmologists. Compact DL model area under the receiver operator characteristic curve was 0.93 (0.01) following five-fold cross-validation. Compact DL model agreement (Kappa) were 0.58, 0.69 and 0.69 for high specificity, balanced sensitivity/specificity and high sensitivity operating points compared to an inter-grader agreement of 0.59. Compact DL gradability model performance was favourable compared to ophthalmologists. Compact DL models can effectively classify non-mydriatic, handheld retinal image gradability with potential applications within community-based DR screening.

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.

Feline ocular toxoplasmosis: seroprevalence, diagnosis and treatment outcome of 60 clinical cases.

Toxoplasmosis is one of the most important protozoa zoonotic diseases worldwide. The present study describes the clinical, seroprevalence findings with ocular toxoplasmosis and the outcome of medicinal treatment of these cats. This study was carried out on 105 cats with various ocular signs, no historical evidence of ocular trauma or drug/vaccine exposure for at least 3 months prior to admission, and without clinical or laboratory evidence of other systemic diseases. Complete case history, physical and ophthalmic examinations were carried out. The seroprevalence of Toxoplasma gondii antibodies was determined using the Toxoplasma Ab Rapid Test and Enzyme Linked Immunosorbent Assay. Out of 105 examined cats with ocular lesions, 60 cats representing 57.14% were seropositive to T. gondii. Out of these 60 cats, 15 cats (25%) had bilateral ocular abnormalities, 25 cats (41.67%) had right-sided ocular disease, and 20 cats (33.33%) had left-sided ocular disease. There were 38 cats (63.33%) with anterior uveitis, 12 cats (20%) with posterior segment involvement, 5 cats (8.33%) with anterior uveitis and anterior chamber abnormalities, 3 cats (5%) with corneal abnormalities and 2 cats (3.34%) with anterior uveitis with concurrent corneal involvement. There was a significant difference in the index values of IgM and IgG between seropositive and seronegative cats with T. gondii antibodies (p⟨0.05). There was no significant difference between the different ages, genders and breeds of cats with seroprevalence of T. gondii antibodies as well as between the age and total number of cats with seropositive and seronegative T. gondii. Out of 60 treated cats, 28 cats (46.7%), 25 cats (41.7%) and 7 cats (11.6%) showed complete, partial and poor response to treatment, respectively. In conclusion, cats showing ocular signs without obvious etiology should be examined serologically for toxoplasmosis and the seropositive cats should be treated with both specific topical and systemic treatments.

Assessing the Clinical Requirement of 2.5% Phenylephrine for Diagnostic Pupil Examination.

Purpose: To evaluate whether the standard dilating drop regimen consisting of phenylephrine, tropicamide, and proparacaine produces clinically significant improvement in pupil size compared to tropicamide and proparacaine during diagnostic eye examination. Methods: Sixty-three adult patients at Washington University School of Medicine Eye Clinic were enrolled in this prospective, randomized trial. Each patient received one of two dilating drop regimens: phenylephrine + tropicamide + proparacaine (PE+T+PP), which is considered the standard therapy, or tropicamide + proparacaine (T+PP). Main outcome measures were the proportion of pupils able to achieve successful clinical examination without need for additional dilating drops and change in predilation to postdilation pupil size. Comparisons were made using McNemar's test, repeated measures analysis of variance, and Fisher's test to determine whether PE is a necessary component of the standard eye examination. Results: There were no statistically significant differences between the PE+T+PP and T+PE treatment groups in predilation to postdilation changes in average resting pupil size (1.58 ± 0.66 and 2.61 ± 0.79; P = 0.57) or constricted pupil size (2.52 ± 0.93 and 3.56 ± 0.96; P = 0.15). There was no statistically significant difference between patients who obtained a successful dilated pupil examination between those receiving PE+T+PP and those receiving T+PP as determined by the examining physicians (Fisher's, P = 0.67). Conclusion: The addition of phenylephrine to tropicamide and proparacaine did not improve pupillary dilation size or ability to conduct a clinical examination. A single dilating agent using tropicamide should be considered in clinical practice.

Choroidal and Retinal Changes After Systemic Adrenaline and Photodynamic Therapy in Non-Human Primates.

Purpose: To determine the tomographic, angiographic, and histologic changes in the choroid and retina of cynomolgus monkeys after systemic adrenaline and verteporfin photodynamic therapy (vPDT). Methods: Six cynomolgus monkeys (12 eyes) were treated with vPDT only (n = 2), adrenaline only for eight weeks (n = 2), adrenaline for eight weeks with vPDT at week 4 (n = 4), and adrenaline for 12 weeks and vPDT at week 8 (n = 4). Spectral-domain optical coherence tomography, angiography, and autofluorescence were performed at baseline and every 14 days thereafter until 28 days after adrenaline therapy or vPDT. Choroid parameters included choroidal thickness (CT) changes and structural changes using semiautomated image binarization. Histology with light and electron microscopy was performed. Results: Adrenaline resulted in subfoveal CT increase at week 4 compared with baseline (3.4%, P = 0.010), with further increase at week 8 (3.9%, P = 0.007). This correlated with choroidal luminal area increase (16.0% at week 8 compared with baseline, P = 0.030). Outer retinal changes included subretinal fluid, ellipsoid zone (EZ) disruption, photoreceptor elongation, and sub/intraretinal bright dots. Hypocyanescent spots surrounded by leakage was observed. Histology showed dilated choroidal vessels, intracytoplasmic vacuoles, and retinal pigment epithelium (RPE) enlarged basal infoldings. The vPDT decreased subfoveal CT at four weeks after vPDT (-7.5%, P = 0.007). This correlated with choroidal stromal area decrease (-18.0%, P < 0.010). Within the treatment spot, there was outer retinal atrophy, EZ disruption, irregular RPE thickening, intense hypoautofluorescence, hyperfluorescence, and hypocyanescence. On histology, there were outer retina, RPE, and choroid changes. Conclusions: Adrenaline induces choroidal vessel dilation and CT increase. The vPDT decreases CT because of a reduction in choroidal stromal component.

Prediction of cycloplegic refraction for noninvasive screening of children for refractive error.

Detection of refractive error in children is crucial to avoid amblyopia and its impact on quality of life. We here performed a retrospective study in order to develop prediction models for spherical and cylinder refraction in children. The enrolled 1221 eyes of 617 children were divided into three groups: the development group (710 eyes of 359 children), the validation group (385 eyes of 194 children), and the comparison group (126 eyes of 64 children). We determined noncycloplegic and cycloplegic refraction values by autorefractometry. In addition, several noncycloplegic parameters were assessed with the use of ocular biometry. On the basis of the information obtained from the development group, we developed prediction models for cycloplegic spherical and cylinder refraction in children with the use of stepwise multiple regression analysis. The prediction formulas were validated by their application to the validation group. The similarity of noncycloplegic and predicted refraction to cycloplegic refraction in individual eyes was evaluated in the comparison group. Application of the developed prediction models for spherical and cylinder refraction to the validation group revealed that predicted refraction was significantly correlated with measured values for cycloplegic spherical refraction (R = 0.961, P < 0.001) or cylinder refraction (R = 0.894, P < 0.001). Comparison of noncycloplegic, cycloplegic, and predicted refraction in the comparison group revealed that cycloplegic spherical refraction did not differ significantly from predicted refraction but was significantly different from noncycloplegic refraction, whereas cycloplegic cylinder refraction did not differ significantly from predicted or noncycloplegic values. Our prediction models based on ocular biometry provide estimates of refraction in children similar to measured cycloplegic spherical and cylinder refraction values without the application of cycloplegic eyedrops.

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.