Diagnostic capabilities of ChatGPT in ophthalmology.

PURPOSE: The purpose of this study is to assess the diagnostic accuracy of ChatGPT in the field of ophthalmology. METHODS: This is a retrospective cohort study conducted in one academic tertiary medical center. We reviewed data of patients admitted to the ophthalmology department from 06/2022 to 01/2023. We then created two clinical cases for each patient. The first case is according to the medical history alone (Hx). The second case includes an addition of the clinical examination (Hx and Ex). For each case, we asked for the three most likely diagnoses from ChatGPT, residents, and attendings. Then, we compared the accuracy rates (at least one correct diagnosis) of all groups. Additionally, we evaluated the total duration for completing the assignment between the groups. RESULTS: ChatGPT, residents, and attendings evaluated 126 cases from 63 patients (history only or history and exam findings for each patient). ChatGPT achieved a significantly lower accurate diagnosis rate (54%) in the Hx, as compared to the residents (75%; p < 0.01) and attendings (71%; p < 0.01). After adding the clinical examination findings, the diagnosis rate of ChatGPT was 68%, whereas for the residents and the attendings, it increased to 94% (p < 0.01) and 86% (p < 0.01), respectively. ChatGPT was 4 to 5 times faster than the attendings and residents. CONCLUSIONS AND RELEVANCE: ChatGPT showed low diagnostic rates in ophthalmology cases compared to residents and attendings based on patient history alone or with additional clinical examination findings. However, ChatGPT completed the task faster than the physicians.

Micro chromosomal deletions at the NYS7 locus and autosomal dominant nystagmus.

Nystagmus is an ocular condition characterized by bilateral involuntary ocular oscillation which can severely affect vision. When not associated with other ocular or systemic diseases, it is referred to as idiopathic or congenital motor nystagmus (CMN). Genome-wide linkage studies have previously identified several loci associated with CMN, however the genes responsible for some of these loci have yet to be identified. We have examined a large, five-generation family with autosomal dominant CMN. Our purpose was to characterize the clinical manifestations and reveal the molecular basis of the disease in this family. In addition to full ophthalmic examination and imaging, molecular analysis included copy number variation analysis, linkage studies, and Sanger sequencing. Expression analyses of candidate genes was done by real-time PCR. Of the 68 family members, 27 subjects in five-generations had CMN, in line with an autosomal dominant inheritance pattern. Molecular analysis was performed on 27 members, 15 of them affected by CMN. Copy number variation analysis using array comparative genomic hybridization (aCGH) revealed a novel deletion located on 1q32 (NYS7) among affected individuals. Linkage analysis using polymorphic markers demonstrated full segregation with a heterozygous haplotype in all affected patients, with a LOD score of >5. Sanger sequencing of affected subjects revealed a novel deletion of 732,526 bp in the linkage interval. No protein-coding genes exist within the deleted region; however, the deletion disrupts topologically associated domains encompassing the gene NR5A2 and the non-protein coding MIR181A. Both are strongly associated with other genes expressed in the retina such as PROX1, which in turn is also associated with genes related to nystagmus such as PAX6. We therefore hypothesized that the deletion might affect NR5A2 and MIR181A expression, causing CMN. Expression analysis by real-time PCR showed significantly lower expression of NR5A2, and significantly higher expression of PROX1 among patients compared with controls. To conclude, among a large five-generation family with autosomal dominant CMN, a large deletion in the interval of NYS7 was linked with the disease. No protein-coding genes exist inside the deleted region, and so the exact mechanism in which CMN is caused is uncertain. Based on topological association and expression analyses we suggest a possible mechanism for the pathogenesis.

Technical failure rates for biometry between swept-source and older-generation optical coherence methods: a review and meta-analysis.

PURPOSE: Precise ocular measurements are fundamental for achieving excellent target refraction following both cataract surgery and refractive lens exchange. Biometry devices with swept-source optical coherence tomography (SS-OCT) employ longer wavelengths (1055-1300 nm) in order to have better penetration through opaque lenses than those with partial coherence interferometry (PCI) or low-coherence optical reflectometry (LCOR) methods. However, to date a pooled analysis showing the technical failure rate (TFR) between the methods has not been published. The aim of this study was to compare the TFR in SS-OCT and in PCI/LCOR biometry. METHODS: PubMed and Scopus were used to search the medical literature as of Feb 1, 2022. The following keywords were used in various combinations: optical biometry, partial coherence interferometry, low-coherence optical reflectometry, swept-source optical coherence tomography. Only clinical studies referring to patients undergoing routine cataract surgery, and employing at least two (PCI or LCOR vs. SS-OCT) optical methods for optical biometry in the same cohort of patients were included. RESULTS: Fourteen studies were included in the final analysis, which presented results of 2,459 eyes of at least 1,853 patients. The overall TFR of all included studies was 5.47% (95% confidence interval [CI]: 3.66-8.08%; overall I2 = 91.49%). The TFR was significantly different among the three methods (p < 0.001): 15.72% for PCI (95% CI: 10.73-22.46%; I2 = 99.62%), 6.88% for LCOR (95% CI: 3.26-13.92%; I2 = 86.44%), and 1.51% for SS-OCT (95% CI: 0.94-2.41%; I2 = 24.64%). The pooled TFR for infrared methods (PCI and LCOR) was 11.12% (95% CI: 8.45-14.52%; I2 = 78.28%), and was also significantly different to that of SS-OCT: 1.51% (95% CI: 0.94-2.41%; I2 = 24.64%; p < 0.001). CONCLUSIONS: A meta-analysis of the TFR of different biometry methods highlighted that SS-OCT biometry resulted in significantly decreased TFR compared to PCI/LCOR devices.

Risk factors for a phacodonesis surprise during cataract surgery in patients with pseudoexfoliation.

PURPOSE: To evaluate the association of different pre-operative parameters with surprise phacodonesis during cataract surgery among patients with pseudoexfoliation (PXF). MATERIALS AND METHODS: This is a retrospective charts review of all PXF patients who underwent cataract surgery between the years 2013 and 2018. Pre-operative parameters (demographics, biometry, intraocular pressure (IOP), endothelial cell count, pupil size, cataract density, glaucoma status, cup to disc ratio, number of glaucoma medications, prior intra-vitreous injections, risk for intraoperative floppy iris syndrome) were compared between patients with and without surprise phacodonesis. Binary logistic regression was used to calculate the predictive value of each parameter. RESULTS: Out of 396 surgical cases with computerized pre-operative assessment, we included 127 eyes of 120 PXF patients without evidence of phacodonesis preoperatively. The mean age was 77.8 ± 12.0 years, 63 (52.7%) were male, and 106 (84.2%) underwent phacoemulsification surgery. We identified 10 cases of surprise phacodonesis during surgery (8.2%). Compared to PXF cases without intraoperative phacodonesis, they had higher pre-operative IOP (23.0 ± 11.0 mmHg vs. 14.9 ± 3.8 mmHg, p < 0.001) and a higher rate of B scan use due to dense cataract obscuring posterior pole evaluation [4 (40%) vs. 15 (12.8%), p = 0.04]. Multivariant binary logistic regression confirmed that only baseline IOP contributed to the prediction of surprise phacodonesis (OR 1.22 CI 1.04-1.43, p = 0.014). CONCLUSIONS: Among patients with PXF undergoing cataract surgery, elevated IOP and poor posterior segment visibility requiring B scan use were associated with zonular instability putting these patients at risk for intra-operative complications.

Application of Nd:YAG laser to the anterior vitreous in malignant glaucoma - a systemic review and meta-analysis.

PURPOSE: The study aims to review the efficacy, safety, and technique of Nd:YAG laser vitreolysis for the management of malignant glaucoma (MG). METHODS: We performed a search of electronic databases for all published studies which included technical specifications of Nd:YAG laser application for MG. Individual patient data was extracted and evaluated in a weighted pooled analysis. RESULTS: Thirty eyes were reported on from seven studies worldwide. Age of affected patients ranged between 37 and 82 years. Nd:YAG vitreolysis was performed either through an iritodomy (66.7%, 18/27 eyes), transpupillary (18.5%, 5/27 eyes), or through both simultaneously (14.8%, 4/27 eyes). Treatment intensity ranged between 1.0 and 11.00 mJ with 75.9% (22/29 eyes) of treatments being 3.0 mJ or lower. Between 1 and 41 pulses per session were applied. Rates of both anatomical and intraocular pressure resolution were examined. Overall, in a pooled analysis, 77% of eyes demonstrated MG resolution with no further treatment required after Nd:YAG vitreolysis (95% CI: 58.1 to 91.4%). A trend for lower need of additional interventions was seen with transpupillary application (11.1% versus 42.1%). No complications were reported. CONCLUSIONS: Nd:YAG laser vitreolysis is a safe procedure, associated with MG resolution in the majority of reported cases, regardless of treatment intensity. Transpupillary treatment may be associated with lower risk of re-intervention.

Preoperative atropine and non-steroidal anti-inflammatory drugs for the prevention of intraoperative floppy iris syndrome.

PURPOSE: To examine the efficacy of preoperative administration of topical atropine 1% and non-steroidal anti-inflammatory drugs (NSAIDs) for prevention of intraoperative floppy iris syndrome (IFIS). METHODS: In this retrospective cohort study, patients who underwent cataract surgery by phacoemulsification between July 2019 and February 2020 in two hospitals were included. Both hospitals are located in central Israel, have similar patient demographics and employ similar surgical techniques. They, however, differ in policy of IFIS prevention. In Meir Medical Center no preventive medications are given pre-operatively, while in Shamir Medical Center patients at-risk for IFIS receive topical atropine 1% once daily and non-steroidal anti-inflammatory drugs (NSAIDs) thrice daily for 3 days preoperatively. RESULTS: Overall, 207 eyes of 207 patients with history of alpha-antagonist use were included. Mean age was 74.9 ± 7.8 years and 82.1% (n = 170) were male. Among patients from the pretreating center 86.8% (n = 92/106) were pre-treated with either NSAIDs or atropine preoperatively, while in the non-pretreating center no treatment was prescribed (n = 0/101). IFIS rate among the non-pretreating center was 29.7% (n = 30/101) compared to 15.1% (n = 16/106) in the pretreating center (p = 0.012). When strictly comparing treated to untreated patients, the treated group had an IFIS rate of 12.0% compared to 30.4% among untreated (p = 0.001). Adjusted for age and gender results remain consistent (odds ratio 0.329 for treated patients, 95% confidence interval: 0.150-0.720; p = 0.005). CONCLUSIONS: IFIS rates were significantly lower in the pretreating center compared to the non-pretreating center. When comparing strictly treated to untreated patients, differences were even more pronounced.

Mammalian target of rapamycin inhibitors for the treatment of astrocytic hamartoma in tuberous sclerosis complex (TSC).

PURPOSE: Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder. Fifty percent of patients with TSC will develop retinal astrocytic hamartoma (RAH). The mammalian target of rapamycin (mTOR) inhibitors interferes with the pathological mechanisms of TSC. Treatment of RAH with mTOR inhibitors has been described in only a few isolated case reports. The purpose of this study was to assess the effect of mTOR inhibitors on RAH in a small cohort of patients. METHODS: The medical records of all consecutive patients with ocular manifestations of TSC that were treated with mTOR inhibitors at the Sheba Medical Center from January 2014 to December 2018 were retrospectively reviewed. Data collection included demographics, medical history, ocular presentation, ocular treatment, and treatment outcome. Tumor size was assessed by a masked observer, before and after treatment. Lesion measurements were made with Heidelberg SD-OCT (HRA + OCT SPECTRALIS), and fundus photos were taken with RetCam3® (Natus, USA) and analyzed by "ImageJ" software. RESULTS: Eleven patients with tuberous sclerosis and astrocytic hamartoma were treated with mTOR inhibitors in the study period. Of them, 6 children (11 eyes, 20 tumors) had proper imaging of tumor size before and after treatment. The analysis included these 11 eyes. All six patients had non-ocular manifestations of TSC, including dermatologic (n = 5), neurologic (n = 5), and renal (n = 3) involvement. Ocular involvement included in five eyes (45%) tumors near the optic disc and in four eyes (37%) foveal tumors. The mean follow-up duration was 2.15 ± 1.4 years (range 10 months to 4.5 years). The average tumor base reduction in the treated group was 17.8% ± 15.9. The average maximal thickness at baseline was 414 ± 174 µm (range 152-686 µm). There was a 14% ± 7.1 reduction after treatment. None of the tumors showed evidence of growth at the final follow-up. CONCLUSION: The findings of this study suggest that mTOR inhibitors can reduce tumor size and that they can be considered as an optional treatment in certain conditions. This preliminary report is the first to quantitatively assess pre- and posttreatment tumor size, in young patients.

The Effect of Blue-Light Filtering Intraocular Lenses on the Development and Progression of Neovascular Age-Related Macular Degeneration.

PURPOSE: To assess the effect of blue-light filtering (BLF) intraocular lenses (IOLs) on the prevention of neovascular age-related macular degeneration (nAMD) after cataract surgery. DESIGN: Cohort study. PARTICIPANTS: Patients who underwent uneventful cataract surgery between 2007 and 2018 at the Ophthalmology Unit of Kymenlaakso Central Hospital, Kotka, Finland. METHODS: Subsequent nAMD rates were compared between patients who received BLF IOLs and those who received non-BLF IOLs. Kaplan-Meier and Cox regression analyses for the overall risk of nAMD developing were assessed. Best-corrected visual acuity (BCVA), foveal thickness, treatment interval, and total number of intravitreal injections were secondary outcomes. A separate analysis was performed on patients with pre-existing nAMD to assess the effect of BLF IOLs on nAMD progression. A single eye of each patient was included. MAIN OUTCOME MEASURE: Neovascular age-related macular degeneration-free survival. RESULTS: Included were 11 397 eyes of 11 397 patients with a mean age of 75.4 ± 8.3 years (62.5% women). The BLF IOL was used in 5425 eyes (47.6%), and the non-BLF IOL was used in 5972 eyes (52.4%). During follow-up (BLF IOL group, 55.2 ± 34.1 months; non-BLF IOL group, 50.5 ± 30.1 months; P < 0.001), 164 cases of new-onset nAMD were recorded (BLF group, n = 88; non-BLF group, n = 76). The nAMD-free survival was similar between the groups (P = 0.465, log-rank test). In a Cox regression analysis controlling for age, gender, and a documented diagnosis of macular degeneration, the use of a BLF IOL was not predictive of nAMD development (hazard ratio [HR], 1.075; 95% confidence interval [CI], 0.79-1.47; P = 0.652). In nAMD patients, secondary clinical outcomes at 1 year were comparable for BCVA (0.57 ± 0.4 logarithm of the minimum angle of resolution vs. 0.45 ± 0.4 logarithm of the minimum angle of resolution; P = 0.136), foveal thickness (285 ± 109 µm vs. 299 ± 103µm; P = 0.527), number of anti-vascular endothelial growth factor injections (6.5 ± 2.5 vs. 6.2 ± 2.7; P = 0.548), and treatment interval (7.5 ± 2.4 weeks vs. 8.1 ± 2.4 weeks; P = 0.271) for BLF and non-BLF IOLs, respectively. Similarly to patients in whom nAMD developed after the surgery, among patients with nAMD before surgery (BLF, n = 71; non-BLF, n = 74), the clinical outcomes again were comparable (all P > 0.05). CONCLUSIONS: In a large cohort of patients who underwent cataract surgery, the use of a BLF IOL resulted in no apparent advantage over a non-BLF IOL in the incidence of nAMD or its progression, nor in clinical variables related to nAMD severity.

Preoperative ocular characteristics predicting the development of intraoperative floppy iris syndrome regardless of alpha-antagonist exposure status.

PURPOSE: To assess structural risk factors for intraoperative floppy iris syndrome (IFIS) available on preoperative examination before cataract surgery. METHODS: In this retrospective study, medical records of patients who underwent cataract surgery in Shamir Medical Center, between July and September 2019, were reviewed. Patients younger than 50 years, with preexisting ocular conditions affecting the pupillary size or anterior chamber depth (ACD), and combined procedures were excluded. Association of IFIS with preoperative ocular parameters was tested using uni- and multivariant analyses. RESULTS: Overall, 394 eyes of 394 patients were included. The mean age was 72.48 ± 8.63 years, and 58.4% were female. IFIS occurred in 18 eyes (4.6%), seven (38.89%) of which had been previously treated with alpha-antagonists. Patients in the IFIS group were significantly older compared with those in the non-IFIS group (78.1 ± 6.7 vs. 72.2 ± 8.6 years, P = 0.005), with no significant gender difference. The mydriatic pupil diameter was significantly smaller in the IFIS group (5.73 ± 1.16 vs. 6.97 ± 1.03 mm, P < 0.001), and the lens thickness (LT) was larger (4.93 ± 0.42 vs. 4.49 ± 0.42 mm, P = 0.001). ACD was inversely correlated with LT (r = - 0.613, P < 0.001) and positively correlated with pupil diameter (r = 0.252, P < 0.001). On univariate analysis, ACD was significantly shallower in the IFIS group (2.88 ± 0.49 vs. 3.14 ± 0.39 mm, P = 0.008). In multivariant analysis controlling for alpha-antagonist use, both LT and mydriatic pupil diameter remained significantly predictive of IFIS (LT: OR 9.9, 95%CI 1.9-49, P = 0.005; pupil diameter OR 0.427, 95%CI 0.26-0.69, P < 0.001). CONCLUSIONS: Increased LT and decreased mydriatic pupil diameter were associated with increased IFIS risk regardless of alpha-antagonist treatment status.

Interdigitation and Ellipsoid Zones Disruption Correlate with Visual Outcomes among Treatment-Naive Patients with Diabetic Macular Edema.

INTRODUCTION: We have recently shown that defects in interdigitation and ellipsoid zones (IZ and EZ) can predict response to anti-VEGF therapy in a small group of treatment-naive diabetic macular edema (DME) patients. The aim of the current study is to further evaluate this association in a larger study group of patients over a longer follow-up time. METHODS: Thirty eyes of 30 treatment-naive DME patients were analyzed in this retrospective study. The integrity of foveal IZ and EZ was evaluated using optical coherence tomography at the diagnosis of DME and following anti-VEGF injections. The defect size was correlated with best-corrected visual acuity (BCVA) and central macular thickness (CMT). RESULTS: The mean patients' age at baseline was 63.0 ± 10.0 years. Patients underwent 3.9 ± 2.9 anti-VEGF injections for a mean of 9.1 ± 4.8 months. Following treatment, the mean Snellen visual acuity (VA) improved from 20/52 to 20/44 (p = 0.05), CMT decreased from 432.5 ± 141.4 µm to 375.2 ± 121.4 µm (p = 0.05) and IZ/EZ defect size decreased from 259.83 ± 375.94 µm to 65.34 ± 143.97 µm (p = 0.001). In patients with no IZ/EZ defects at baseline, the mean Snellen VA was better when compared to those with IZ/EZ defects (20/36 vs. 20/70, p = 0.031). The number of eyes with IZ/EZ defects decreased from 17 (57%) at baseline to 6 (20%) at end of follow-up (p < 0.01). BCVA gain correlated with IZ/EZ defect size reduction (r = 0.41, p = 0.02) but not with improvement in CMT (r = 0.28, p = 0.121). CONCLUSIONS: IZ/EZ defect size correlated not only with baseline BCVA but also predicted the change in BCVA after anti-VEGF treatment. Possible future automatic measurement of IZ/EZ defect size might prove helpful for the evaluation of treatment response.

Agreement of Corneal Endothelial Cell Analysis Between Konan-Noncon Robo SP-6000 and Tomey EM-3000 Specular Microscopes in Healthy Subjects.

PURPOSE: To compare corneal endothelium parameters taken by two common noncontact specular microscopes in healthy subjects. METHODS: Healthy participants visiting the outpatient eye clinic at the Rabin Medical Center, Petah Tikva, Israel, were recruited prospectively. All participants underwent three consecutive corneal endothelial cell photographs with both the Konan-Noncon Robo SP-6000 and the Tomey EM-3000 specular microscopes. Endothelial cell density (ECD) was evaluated using the manual center technique in both machines. Bland-Altman graphs were used to assess the agreement between the devices, and intraclass correlation coefficient (ICC) served to assess intraobserver variability for each device. RESULTS: Recruited were 49 healthy subjects with a mean age of 48.9±15.6 years, 49 right eyes were included. The mean ECD was comparable between the Tomey EM-3000 and the Konan-Noncon Robo SP-6000 (2,713.2±242.4 vs. 2,700.8±300.5 cells/mm2, respectively, P=0.47) with a mean difference of 12.4 cells/mm2 (0.67%), a mean ECD absolute difference of 93.3 cells/mm2, and low 95% limits of agreement of -222.0 to +246.9 cells/mm2. A folded empirical distribution function curve showed that all differences fell within 525.4 cells/mm2, centered around a median of 13.3 cells/mm2. Intraclass correlation coefficient was high for both the Konan-Noncon Robo SP-6000 (0.93, 95% confidence interval [CI]: 0.89-0.95) and the Tomey EM-3000 (0.88, 95% CI: 0.82-0.93). CONCLUSIONS: The difference in endothelial cell measurements between the Konan SP-6000 and the Tomey EM-3000 specular microscopes through the center and the L-count analyzing techniques, respectively, is clinically small and not statistically significant. Nevertheless, caution should be taken when used interchangeably because ECD difference between the two machines can be as high as 525.4 cells/mm2.

Ocular involvement in coronavirus disease 2019 (COVID-19): a clinical and molecular analysis.

PURPOSE: Coronavirus disease 2019 (COVID-19) caused a global pandemic with millions infected worldwide. Little is known on the ocular involvement associated with the disease. The aim of this study was to assess the clinical and molecular ocular involvement among patients with confirmed COVID-19 admitted to a tertiary care facility. METHODS: Consecutive patients admitted to the COVID-19 Ward of the Shamir Medical Center in Israel during March and April, 2020 were included. The control group included patients negative for COVID-19 admitted during a similar period to a different ward. Patients were examined by trained Ophthalmologists. SARS-CoV-2 conjunctival swab samples were obtained. RESULTS: Included were 48 patients, 16 with confirmed COVID-19 and 32 controls. Median patient age was 68.5 (interquartile range: 31.5, mean: 63 ± 21) years and 48% were male. Active conjunctival injection was present in three patients (19%) with COVID-19, compared to none in the controls (p = 0.034). Patients with COVID-19 were more likely to complain of foreign body sensation (31.3% vs 3.1%, p = 0.005) and redness of the eye (25% vs 0%, p = 0.003). Conjunctival injection was associated with loss of smell and taste (75% vs 7.7%, p = 0.018). Viral conjunctival swab tests all showed negative results for all three viral genes tested (E, N, and RdRp). CONCLUSIONS: Among patients admitted to a tertiary referral center with confirmed COVID-19, active conjunctival injection was noted in one out of five cases, and was associated with loss of smell and taste. Conjunctival swabs for viral RNA were negative in patients with and without ocular involvement.

The effect of hemodialysis on individual retinal layer thickness.

PURPOSE: The aim of this study was to employ newly developed advanced image analysis software to evaluate changes in retinal layer thickness following hemodialysis. METHODS: A non-randomized prospective study of patients with end-stage renal disease assessed on the same day before and after hemodialysis. Intraocular pressure and central corneal thickness were analyzed, and spectral domain optical coherence tomography results were automatically segmented using the Orion software and then compared. All patients had normal retinal optical coherence tomography findings before hemodialysis. RESULTS: Of the 31 suitable end-stage renal disease patients treated with hemodialysis who provided consent to participate, seven were unable to complete all evaluations, leaving 24 patients for analysis in the final study group. Their mean age was 66.67±14.3 years (range: 35-88), and 62.5% were males. Mean central corneal thickness did not change following hemodialysis (563.4±30.2 µm to 553.1±47.2 µm, p=.247), while mean intraocular pressure decreased (14.48±2.5 mmHg to 13.16±2.28 mmHg, p=.028). Individual mean retinal layer thickness showed no significant change, including the retinal nerve fiber layer (40.9±6.8 µm to 40.1±5.2 µm, p=.412), the ganglion cell and the inner plexiform layer (68.66±8 µm to 69.03±7.6 µm, p=.639), and the photoreceptor layer (50.26±2.8 µm to 50.32±3.1 µm, p=.869). Total retinal thickness similarly remained constant, with a mean of 303.7±17.3 µm before and 304.33±18.4 µm after hemodialysis (p=.571). CONCLUSIONS: Thickness of retinal layers, as assessed by individual segmentation, and central corneal thickness were not affected by hemodialysis treatment, while intraocular pressure was significantly reduced among patients with end-stage renal disease without pre-existing ocular pathology who were undergoing hemodialysis. These results support the view that hemodialysis does not have a negative impact on the retinal morphology of end-stage renal disease patients, who comprise a population with high rates of diabetic and/or hypertensive retinopathy as well as vision-threatening complications.

FOXC1 variant in a family with anterior segment dysgenesis and normal-tension glaucoma.

Our study describes the glaucoma phenotype in a family with Axenfeld-Rieger syndrome (ARS) and a FOXC1 variant. Included were 20 subjects from a large three generation family of Jewish Indian ancestry. Subjects underwent a comprehensive ophthalmic examination including automated perimetry and optical coherence tomography. Eight subjects were available for molecular analysis which included whole genome sequencing on selected patients and Sanger sequencing for variant screening. Eleven patients demonstrated a wide spectrum of Axenfeld-Rieger anomaly signs and symptoms. These ranged from subtle angle abnormalities to remarkable anterior segment abnormalities such as corectopia, iris adhesions and strands. Among them, six had glaucoma and two were glaucoma suspects. Of the six subjects with glaucoma three had high-tension glaucoma and two had normal-tension glaucoma. Molecular analysis revealed a previously described pathogenic variant in the FOXC1 gene (c.378C > G p.I126M; rs104893958), in six affected patients which was not identified in two healthy siblings. Molecular analysis also revealed a PITX2 missense variant (c.28T > A p.L10M; rs755864040) which did not segregate with clinical findings and was considered likely benign. In conclusion, patients with ARS due to FOXC1 variants may present with glaucomatous optic nerve damage without apparent elevation in IOP. Normal-tension glaucoma is less commonly reported in individuals with ARS and a comprehensive glaucoma assessment may be warranted in these individuals even with normal IOP. These findings raise the possibility that glaucomatous damage associated with FOXC1 is not only due to high IOP.

The pathogenicity of SLC38A8 in five families with foveal hypoplasia and congenital nystagmus.

PURPOSE: A recently described subtype of foveal hypoplasia with congenital nystagmus and optic-nerve-decussation defects was found to be associated with mutations in the SLC38A8 gene. The aim of this study is to advance the clinical and molecular knowledge of SLC38A8 gene mutations. METHODS: Five Israeli families with congenital foveal hypoplasia were studied, two of Karait Jewish origins and three of Indian Jewish origins. Subjects underwent a comprehensive ophthalmic examination including retinal photography and ocular coherence tomography. Molecular analysis including whole exome sequencing and screening of the SLC38A8 gene for specific disease-causing variants was performed. RESULTS: Eight affected individuals were identified, all had congenital nystagmus and all but one had hypoplastic foveal pits. Anterior segment dysgenesis was observed in only one patient, one had evidence of developmental delay and another displayed early age-related macular degeneration (AMD). Molecular analysis revealed a recently described homozygous mutation, c.95T > G; p.Ile32Ser, in two families of Jewish Indian descent, and the same mutation in two families of Karaite Jewish descent. In a patient with only one pathogenic mutation (c.95T > G; p.Ile32Ser), a possible partial clinical expression of the disorder was seen. One patient of Jewish Indian descent was found to be compound heterozygous for c.95T > G; p.Ile32Ser and a novel mutation c.490_491delCT; p.L164Vfs*41. CONCLUSIONS: In five unrelated families with congenital nystagmus and foveal hypoplasia, mutations in the SLC38A8 gene were identified. Possible partial expression in a heterozygous patient was observed and novel potential disease-related phenotypes were identified including early-onset AMD and developmental delay. A novel mutation was also identified and a similar mutation in both Indian and Karaite Jewish ethnicities could be suggestive for common ancestry.

Effect of light and diurnal variation on macular thickness in X-linked retinoschisis: a case series.

BACKGROUND: Diurnal variations in foveal thickness have been reported in several ocular pathologies including X-linked retinoschisis (XLRS), but its underlying mechanism is poorly understood. Rods are active under scotopic conditions with high metabolic demand, and its decrease may have positive effect on metabolic activity and macular thickness. The purpose of this study is to evaluate whether exposure to light and diurnal variation influence macular thickness in XLRS patients. METHODS: Five patients with clinical suspicion of XLRS underwent RS1 gene sequencing and optical coherence tomography measurements at three consecutive times: morning following sleep in a dark room, morning following sleep in an illuminated room, and late afternoon following sleep in an illuminated room. Central macular thickness (CMT) was compared between measurements, and molecular analysis was performed. RESULTS: Five RS1 mutations were identified: p.Gly140Arg, p.Arg141Cys, p.Gly109Glu, p.Pro193Leu, and p.Arg200His in patients 1-5, respectively. Two patients (4-5) had atrophied macula and were excluded from macular thickness variation analysis. A significant decrease in CMT between morning and afternoon measurements was observed in all patients (1-3: mean: 455.0 ± 32 µm to 342.17 ± 39 µm, 25%). Morning measurements following sleep in an illuminated room show a CMT reduction in all eyes of all patients with a mean reduction of 113 µm (mean: 547.17 ± 105 µm to 455.0 ± 32 µm, 17%). CONCLUSIONS: Among XLRS patients, CMT decreased at the afternoon compared to the morning of the same day and may be reduced following sleep in an illuminated room. These results help shed light on the pathophysiologic process underlying intraretinal fluid accumulation involved with the disease.

REDUCTION OF POSTINTRAVITREAL INJECTION PAIN USING ICE: An Open-Label Interventional Randomized Controlled Trial.

PURPOSE: Intravitreal injections of intraocular therapeutic agents are a common and effective treatment for various retinal pathologies. Patient discomfort related to injection is a potential barrier to treatment. Our aim in this study was to evaluate whether cooling the eye using topical ice compresses before intravitreal injection will reduce pain or bleeding. METHODS: This randomized controlled open-label study included 42 patients. All patients received a standard topical anesthesia protocol and then were randomly assigned to either receive a placement of ice packs (intervention group) or a room-temperature pack (control group) on the eyelid, 2 minutes before the intravitreal injection. Patients' discomfort, itching, burning and pain (using visual analog scale), and bleeding size (using photographs) were measured 1 and 10 minutes after the injection. Tolerability was calculated by averaging patients' discomfort, itching, burning, and pain scores. RESULTS: At 1 minute, pain (1.95 vs. 4.27, P = 0.01) and overall tolerability (1.66 vs. 2.98, P = 0.03) were significantly lower in patients receiving ice packs. At 10 minutes, pain (1.6 vs. 3.73, P = 0.02), burning (0.9 vs. 3.09, P = 0.007), discomfort (2.1 vs. 4.27, P = 0.008), and overall tolerability (1.23 vs. 2.87, P = 0.004) were all significantly lower in the ice group compared with the controls. Bleeding size (area or circumference) was not statistical different between groups. CONCLUSION: Topical ice patch administered before intravitreal injection significantly decreased pain and overall tolerability. This simple and inexpensive method may be used to ameliorated pain and improve tolerability.

Association between intraocular lens diopter and posterior capsular opacification.

IMPORTANCE: Posterior capsular opacification (PCO) is the most common complication after cataract surgery. BACKGROUND: We aimed to assess the relationship between intraocular lens (IOL) diopter and formation of PCO among a consecutive real-world registry. DESIGN: Cohort study. PARTICIPANTS: Included were 14 264 consecutive cases of uncomplicated cataract surgery performed during 2014 to 2018 in Helsinki University Hospital in Finland. METHODS: Nd:YAG capsulotomies were used as an estimate of clinically significant PCO. A single eye of each patient and a single type of IOL were included. MAIN OUTCOME MEASURE: Nd:YAG posterior capsulotomy free survival. RESULTS: Mean age was 73.2 ± 9.9 years and 61.8% were female. Mean follow-up time was 25.4 ± 16.8 months. Overall PCO rates were 1.1% at 1-year, 3.0% at 2-year, 7.1% at 3-year and 10.2% at 4-year. Patients with IOL diopters (D) in the lower quartile (≤20.0 D) had significantly higher rates of PCO (1.3% at 1-year, 4.4% at 2-years, 9.4% at 3-years and 14.2% at 4-years, P < .001). A logistic regression model showed increased risk for PCO formation with lower diopter IOLs; for ≤20.0 D: OR 1.343 (95% CI: 1.132-1.593), for ≤10.0 D: OR 2.409 (95% CI 1.203-4.287), P < .001 for all comparisons. In a multivariant regression accounting for possible confounders, results remained consistent. CONCLUSIONS AND RELEVANCE: Among a cohort of patients undergoing cataract surgery, use of lower diopter IOLs was associated with increased incidence of clinically significant PCO. Research into IOL biomechanics to decrease PCO may be warranted especially in lower diopter IOLs.

Clinical outcomes of Ankoris toric intraocular lens implantation using a computer-assisted marker system.

PURPOSE: To report the clinical outcomes of patients who underwent cataract surgery with implantation of Ankoris monofocal toric intraocular lens (IOL) (PhysIOL SA, Liège, Belgium) using the Zeiss Callisto Eye (Carl Zeiss AG, Dublin, CA). METHODS: We conducted a retrospective case series of patients who underwent routine cataract extraction and implantation of Ankoris toric IOL using the Zeiss Callisto eye between January 2018 and December 2018 by four senior surgeons. Patients' medical records were reviewed, and clinical outcomes including postoperative refraction, visual acuity outcomes, IOL position and deviation from planned axis were collected. RESULTS: Fifty-six eyes of 56 patients were included, 48% were female, and the mean age was 70 ± 8 years. Patients with pseudoexfoliation syndrome, glaucoma or keratoconus were excluded from the study. Pre-operative mean corneal astigmatism was 2.38 ± 0.78 diopters (D), and mean implanted IOL cylindrical power was 3.06 ± 1.07 D. IOL rotation 30 days postoperatively was within 5° in 82% of eyes and between 6° and 10° in 10.8% of eyes. Mean postoperative refractive astigmatism 30 days postoperatively was 0.22 ± 0.36 D; in 84% of eyes the postoperative refractive astigmatism was ≤ 0.50 D. IOL rotation significantly increased between day 1 to day 7 postoperatively (1.91 ± 3.15° to 3.18 ± 3.3°, P = 0.001). However, no significant rotation had occurred between day 7 and day 30 postoperatively (P = 0.093). CONCLUSION: Cataract surgery with implantation of Ankoris monofocal toric IOL using the Zeiss Callisto Eye marking system is predictable and effective in reducing refractive astigmatism.

Chorio-retinal toxoplasmosis: treatment outcomes, lesion evolution and long-term follow-up in a single tertiary center.

BACKGROUND: Ocular toxoplasmosis is a common cause of ocular inflammation worldwide. The aim of this study is to characterize the clinical outcomes and lesion evolution of patients with ocular toxoplasmosis and to compare the primary and reactivation subgroups. METHODS: A retrospective population-based cohort study at one uveitis-specialized tertiary referral center. Patients presenting with active ocular toxoplasmosis between the years 2007-2016 were included. Primary ocular toxoplasmosis and reactivations were compared. RESULTS: Included were 22 patients, 64% female with a mean age of 29 ± 18 years, 59% (n = 13) were primary, 9% (n = 2) congenital and 32% (n = 7) reactivations. Visual acuity improved from 0.38 ± 0.44 to 0.20 ± 0.27 LogMAR (P = 0.026) after a mean of 37 ± 33 months. Initial lesion size was 2.38 ± 1.1 optic disc areas, reducing to 1.56 ± 1.24 following 2 months (34% reduction, P = 0.028) and to 1.17 ± 0.87 disc areas following one year (51% reduction, P = 0.012). Patients with macula-threatening lesions had worse visual acuity (0.50 ± 0.46 vs. 0.05 ± 0.07 LogMAR, P = 0.047). Primary and reactivation subgroups had similar presentations, visual outcomes and recurrence rates (all P > 0.05). CONCLUSIONS: In this population, primary ocular toxoplasmosis was the most common presentation. Lesion size reduced during the initial months with limited change thereafter and a third of cases recurred. Macula-threatening lesions were associated with worse visual acuity, and no significant differences were seen between the primary and reactivation subgroups.