EFFICIENCY AND SAFETY OF INTERNAL LIMITING MEMBRANE PEELING WITH DIFFERENT FORCEPS FOR MACULAR DISEASE.

PURPOSE: To compare the efficiency and safety of internal limiting membrane (ILM) peeling between the Sharkskin forceps and End-grasping forceps in various macular diseases. METHODS: It is a prospective cohort block-randomized study conducted in a tertiary medical center. Seventy subjects with macular hole, epiretinal membrane, vitreomacular traction syndrome, or myopic foveoschisis, receiving pars plana vitrectomy and ILM peeling surgery were equally divided into Sharkskin forceps group and End-grasping forceps group. The duration of ILM peeling, the number of attempts to initiate peeling, and peeling-related retinal damage were evaluated by recorded video and optical coherence tomography. RESULTS: In the Sharkskin group, the authors demonstrated significantly fewer attempts to initiate ILM peeling compared with End-grasping group, with an average of 1.9 and 3.1 attempts ( P = 0.0001) and a lower incidence of retinal microstructural damage (20% vs. 45%, P < 0.0001). Moreover, the mean depth of inner retinal injury at the initiating site exhibited distinct difference postoperatively at 3 months between the Sharkskin group then the End-grasping group (4.3 vs. 30.0 µ m, P = 0.001). CONCLUSION: Sharkskin forceps provide better efficiency and outcome in ILM peeling in patients with various vitreomacular interface diseases, including reduced risk of retinal injury and fewer attempts to initiate ILM flap.

Assessment of histological and immunohistochemical features of retinal tissues using a novel tissue submission procedure.

We introduce a novel tissue submission procedure without additional equipment or storage facilities for assessing the histological and immunohistochemical features of retinal tissues. In total, 150 specimens were collected from patients who underwent vitrectomy or macular surgery from January to December 2020. Ninety-eight specimens were submitted using the new procedure, and 58 specimens were submitted as flat-mount slides to compare specimen adequacy. The tissues submitted using the new procedure were subjected to paraffin-embedding and sectioning for hematoxylin & eosin staining. Additional immunohistochemical analysis was performed to assess the cellular composition in retinal tissues with diverse etiologies. The new submission procedure had an adequacy ratio of 75.51%, which was comparable to that of the flat-mount method (p = 0.1397). The new method could produce high-quality images of histological features of tissues and facilitated immunohistochemical analysis to demonstrate cell origins. More glial cells (p = 0.000) and myofibroblasts (p = 0.012) were detected in the epiretinal membranes (ERMs) than in the internal limiting membranes (ILMs). Subgroup analysis revealed that secondary ERMs contained more macrophage-like cells (p = 0.001) and retinal pigment epithelial cells (p = 0.000) than did idiopathic ERMs. Our novel tissue submission procedure can be applied to routine clinical practice. Our study provides additional histological and immunohistochemical evidence of cellular components in retinal tissues based on a large number of human tissue samples. Moreover, tissues submitted using the new method can be permanently preserved, enabling future investigation for potential prognostic or therapeutic targets.

The impact of artificial intelligence on retinal disease management: Vision Academy retinal expert consensus.

PURPOSE OF REVIEW: The aim of this review is to define the "state-of-the-art" in artificial intelligence (AI)-enabled devices that support the management of retinal conditions and to provide Vision Academy recommendations on the topic. RECENT FINDINGS: Most of the AI models described in the literature have not been approved for disease management purposes by regulatory authorities. These new technologies are promising as they may be able to provide personalized treatments as well as a personalized risk score for various retinal diseases. However, several issues still need to be addressed, such as the lack of a common regulatory pathway and a lack of clarity regarding the applicability of AI-enabled medical devices in different populations. SUMMARY: It is likely that current clinical practice will need to change following the application of AI-enabled medical devices. These devices are likely to have an impact on the management of retinal disease. However, a consensus needs to be reached to ensure they are safe and effective for the overall population.

Current status and practical considerations of artificial intelligence use in screening and diagnosing retinal diseases: Vision Academy retinal expert consensus.

PURPOSE OF REVIEW: The application of artificial intelligence (AI) technologies in screening and diagnosing retinal diseases may play an important role in telemedicine and has potential to shape modern healthcare ecosystems, including within ophthalmology. RECENT FINDINGS: In this article, we examine the latest publications relevant to AI in retinal disease and discuss the currently available algorithms. We summarize four key requirements underlining the successful application of AI algorithms in real-world practice: processing massive data; practicability of an AI model in ophthalmology; policy compliance and the regulatory environment; and balancing profit and cost when developing and maintaining AI models. SUMMARY: The Vision Academy recognizes the advantages and disadvantages of AI-based technologies and gives insightful recommendations for future directions.

PREDICTING VISUAL OUTCOME AFTER SURGERY IN PATIENTS WITH IDIOPATHIC EPIRETINAL MEMBRANE USING A NOVEL CONVOLUTIONAL NEURAL NETWORK.

PURPOSE: To develop a deep convolutional neural network that enables the prediction of postoperative visual outcomes after epiretinal membrane surgery based on preoperative optical coherence tomography images and clinical parameters to refine surgical decision making. METHODS: A total of 529 patients with idiopathic epiretinal membrane who underwent standard vitrectomy with epiretinal membrane peeling surgery by two surgeons between January 1, 2014, and June 1, 2020, were enrolled. The newly developed Heterogeneous Data Fusion Net was introduced to predict postoperative visual acuity outcomes (improvement ≥2 lines in Snellen chart) 12 months after surgery based on preoperative cross-sectional optical coherence tomography images and clinical factors, including age, sex, and preoperative visual acuity. The predictive accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the convolutional neural network model were evaluated. RESULTS: The developed model demonstrated an overall accuracy for visual outcome prediction of 88.68% (95% CI, 79.0%-95.7%) with an area under the receiver operating characteristic curve of 97.8% (95% CI, 86.8%-98.0%), sensitivity of 87.0% (95% CI, 67.9%-95.5%), specificity of 92.9% (95% CI, 77.4%-98.0%), precision of 0.909, recall of 0.870, and F1 score of 0.889. The heatmaps identified the critical area for prediction as the ellipsoid zone of photoreceptors and the superficial retina, which was subjected to tangential traction of the proliferative membrane. CONCLUSION: The novel Heterogeneous Data Fusion Net demonstrated high accuracy in the automated prediction of visual outcomes after weighing and leveraging multiple clinical parameters, including optical coherence tomography images. This approach may be helpful in establishing personalized therapeutic strategies for epiretinal membrane management.

Differential characteristics among asymptomatic and symptomatic meibomian gland dysfunction and those with dry eye.

PURPOSE: To identify the characteristics of asymptomatic meibomian gland dysfunction (MGD), symptomatic MGD, and MGD coexisting with dry eye disease (DED). METHODS: This cross sectional study enrolled a total of 153 eyes of 87 MGD patients. Participants filled in ocular surface disease index (OSDI) questionnaires. Age, gender, Schirmer's test, meibomian gland (MG) related parameters, lipid layer thickness (LLT) and blinking were compared among patients with asymptomatic MGD, symptomatic MGD, and MGD with DED. Multivariate regression was used to analyze the significant factor of DED in MGD. Spearman's rank correlation analysis was used to evaluate the association between the significant factors and MG function. RESULTS: There was no difference in age, Schirmer's test, lid changes, MG secretion, and MG morphology among three groups. The OSDI of asymptomatic MGD, symptomatic MGD and MGD coexisting with DED were 8.5 ± 2.9, 28.5 ± 12.8 and 27.9 ± 10.5, respectively. Patients with MGD coexisting with DED exhibited more frequent eye blinking than that of patients with asymptomatic MGD (8.1 ± 4.1 vs. 6.1 ± 3.5 blinks/20 sec, P = 0.022), and reduced LLT than that of patients with asymptomatic MGD (68.6 ± 17.2 vs. 77.6 ± 14.5 nm, P = 0.010) and symptomatic MGD (78.0 ± 17.1 nm, P = 0.015). Multivariate analysis identified LLT (per nm, OR = 0.96, 95% CI = 0.93-0.99, P = 0.002) as a significant factor associated with DED development in MGD. The number of expressible MG was positively correlated with LLT (Spearman's correlation coefficient = 0.299, P = 0.016) but negatively correlated with the number of blinking (Spearman's correlation coefficient = -0.298, P = 0.016) in MGD patients with DED, and these findings were not identified in those without DED. CONCLUSIONS: Asymptomatic MGD, symptomatic MGD, and MGD coexisting with DED share similar characteristics, including meibum secretion and morphology, but MGD patients coexisting with DED exhibited significantly reduced LLT.

Mitochondrial transport mediates survival of retinal ganglion cells in affected LHON patients.

The mutations in the genes encoding the subunits of complex I of the mitochondrial electron transport chain are the most common cause of Leber's hereditary optic neuropathy (LHON), a maternal hereditary disease characterized by retinal ganglion cell (RGC) degeneration. The characteristics of incomplete penetrance indicate that nuclear genetic and environmental factors also determine phenotypic expression of LHON. Therefore, further understanding of the role of mutant mitochondrial nicotinamide adenine dinucleotide dehydrogenase subunit proteins and nuclear genetic factors/environmental effects in the etiology of LHON is needed. In this study, we generated human-induced pluripotent stem cells (hiPSCs) from healthy control, unaffected LHON mutation carrier, and affected LHON patient. hiPSC-derived RGCs were used to study the differences between affected and unaffected carriers of mitochondrial DNA point mutation m.11778G > A in the MT-ND4 gene. We found that both mutated cell lines were characterized by increase in reactive oxygen species production, however, only affected cell line had increased levels of apoptotic cells. We found a significant increase in retrograde mitochondria and a decrease in stationary mitochondria in the affected RGC axons. In addition, the messenger RNA and protein levels of KIF5A in the LHON-affected RGCs were significantly reduced. Antioxidant N-acetyl-L-cysteine could restore the expression of KIF5A and the normal pattern of mitochondrial movement in the affected RGCs. To conclude, we found essential differences in the mutually dependent processes of oxidative stress, mitochondrial transport and apoptosis between two LHON-specific mutation carrier RGC cell lines, asymptomatic carrier and disease-affected, and identified KIF5A as a central modulator of these differences.

Correlations between Clinical and Histopathologic Characteristics in Idiopathic Epiretinal Membrane.

PURPOSE: To investigate correlations between clinical and histopathologic characteristics of idiopathic epiretinal membrane (ERM). DESIGN: Retrospective interventional case series. PARTICIPANTS: In total, 87 eyes from 87 patients with idiopathic ERM who underwent pars plana vitrectomy with peeling of the ERM from 2019 to 2020 were included. METHODS: The outcomes of clinical ophthalmic examination, including measurement of best-corrected visual acuity (BCVA) and spectral-domain OCT (SD-OCT), before and after surgery were reviewed. Surgical specimens were fixed in formalin and embedded in paraffin for histologic and immunohistochemical analysis. MAIN OUTCOMES MEASURES: The association between morphological characteristics revealed on SD-OCT images and the cellular composition of the surgically excised ERM demonstrated with immunohistochemical staining were the main outcome measures. Changes in the BCVA and central macular thickness (CMT) were assessed through a comparison of preoperative and postoperative measurements. RESULTS: Based on SD-OCT morphological characteristics in the foveal area, 15 cases were classified into group 1A (mainly outer retinal thickening), 39 into group 1B (more tenting of the outer retina and distorted inner retina), and 33 into group 1C (prominent inner retina thickening). Overall, postoperative final BCVA and CMT at 1 year improved in all groups. Patients who presented with a better initial BCVA exhibited a more favorable final BCVA. Epiretinal membranes in group 1C demonstrated the greatest decrease in CMT compared with those in groups 1B and 1A, but the final CMT did not differ among the groups. A negative correlation between the density of hyalocytes (P = 0.003) and myofibroblasts (P = 0.047) was noted between the 3 groups. Total cell density and glial cell density of the ERMs were strongly associated with poor final BCVA and BCVA improvement. CONCLUSIONS: The present study provides new histopathologic information regarding the formation and progression of idiopathic ERM. Glial cell proliferation plays a predominant role in these processes. Epiretinal membranes with high cellularity and glial cell density may cause damage to the retina structure, resulting in poor postoperative visual outcomes. These findings provide additional evidence supporting early surgical intervention in patients with idiopathic ERM reported with visual disturbance.

Refractive status, biometric components, and functional outcomes of patients with threshold retinopathy of prematurity: systemic review and a 17-year longitudinal study.

OBJECTIVE: To assess the long-term refractive status, visual outcome, astigmatism, and the change in biometric optic components in older adolescents up to age 17 years with threshold retinopathy of prematurity (ROP) treated with diode laser. METHODS: A retrospective, longitudinal study in which cycloplegic refraction, keratometry, and the biometric measurement of optic components were performed on 28 consecutive preterm eyes with laser-treated threshold ROP at age 17 years. The study results were statistically analysed and compared with age-matched full-term control. RESULTS: All patients with ROP had myopia (average spherical equivalent of - 6.35 D, ranges from - 1.25 to - 12.38 D), and 12 eyes (43%) were highly myopic (spherical equivalent < - 6.0 D). Threshold ROP eyes exhibited a significantly poorer visual acuity (P < 0.001), greater cylinder refractive error (P < 0.001), higher corneal astigmatism (P < 0.001), and flatter horizontal corneal curvature (P = 0.01) compared with age-matched controls. Biometric optic components analysis revealed a significant shallower anterior chamber depth (P < 0.001), thicker lens (P < 0.001), and shorter axial length (P = 0.021) in laser-treated ROP eyes compared with age-matched controls. CONCLUSIONS: In this 17-year longitudinal study, a higher prevalence of myopia and astigmatism was observed in laser-treated threshold ROP eyes compared with age-matched control eyes. Myopia and astigmatism in laser-treated ROP eyes typically progress through adolescence after school age. Therefore, we recommend that preterm patients with laser-treated threshold ROP should attend regular follow-up not only for refractive status but also for structural change of anterior segment until their adolescence.

FACTORS RELATED TO UNFAVORABLE VISUAL OUTCOME AFTER IDIOPATHIC EPIRETINAL MEMBRANE SURGERY IN PATIENTS WITH GLAUCOMA.

PURPOSE: To evaluate the visual outcomes after idiopathic epiretinal membrane surgery in glaucomatous and nonglaucomatous eyes and factors related to unfavorable outcomes in glaucomatous eyes. METHODS: This was a retrospective cohort study including patients undergoing idiopathic epiretinal membrane surgery with ≥12-month follow-up. Final visual acuity at pseudophakic status was compared among groups of glaucoma, glaucoma suspect, and nonglaucoma and correlated with optical coherence tomography and visual field characteristics in patients with glaucoma. RESULTS: Of the 314 patients enrolled, 31 had glaucoma and 22 were glaucoma suspect. Baseline visual acuity and central foveal thickness were similar across the groups. Most patients had improved/stable visual acuity postoperatively, with a lower proportion of 83.9% with glaucoma than 96.9% and 100% without glaucoma and glaucoma suspect, respectively (P = 0.002). The mean visual acuity did not change in the glaucoma group (from 6/29 to 6/23), but it improved from 6/25 to 6/12 (a gain of 16.7 approxETDRS letters) in nonglaucoma and 6/26 to 6/14 in glaucoma suspect (a gain of 14.0 approxETDRS letters) (both P < 0.001). The change of visual acuity was correlated with preoperative visual field defects (P < 0.001, r2 = 0.554). Patients with glaucoma with more advanced, fixation-threatening defects or temporally located inner nuclear layer microcysts were more likely to have worsened visual acuity. CONCLUSION: Visual field testing is imperative for patients with glaucoma before idiopathic epiretinal membrane surgery for outcome assessment.

Expression of Endogenous Angiotensin-Converting Enzyme 2 in Human Induced Pluripotent Stem Cell-Derived Retinal Organoids.

Angiotensin-converting enzyme 2 (ACE2) was identified as the main host cell receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its subsequent infection. In some coronavirus disease 2019 (COVID-19) patients, it has been reported that the nervous tissues and the eyes were also affected. However, evidence supporting that the retina is a target tissue for SARS-CoV-2 infection is still lacking. This present study aimed to investigate whether ACE2 expression plays a role in human retinal neurons during SARS-CoV-2 infection. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids and monolayer cultures derived from dissociated retinal organoids were generated. To validate the potential entry of SARS-CoV-2 infection in the retina, we showed that hiPSC-derived retinal organoids and monolayer cultures endogenously express ACE2 and transmembrane serine protease 2 (TMPRSS2) on the mRNA level. Immunofluorescence staining confirmed the protein expression of ACE2 and TMPRSS2 in retinal organoids and monolayer cultures. Furthermore, using the SARS-CoV-2 pseudovirus spike protein with GFP expression system, we found that retinal organoids and monolayer cultures can potentially be infected by the SARS-CoV-2 pseudovirus. Collectively, our findings highlighted the potential of iPSC-derived retinal organoids as the models for ACE2 receptor-based SARS-CoV-2 infection.

Identification of Novel Genomic-Variant Patterns of OR56A5, OR52L1, and CTSD in Retinitis Pigmentosa Patients by Whole-Exome Sequencing.

Inherited retinal dystrophies (IRDs) are rare but highly heterogeneous genetic disorders that affect individuals and families worldwide. However, given its wide variability, its analysis of the driver genes for over 50% of the cases remains unexplored. The present study aims to identify novel driver genes, disease-causing variants, and retinitis pigmentosa (RP)-associated pathways. Using family-based whole-exome sequencing (WES) to identify putative RP-causing rare variants, we identified a total of five potentially pathogenic variants located in genes OR56A5, OR52L1, CTSD, PRF1, KBTBD13, and ATP2B4. Of the variants present in all affected individuals, genes OR56A5, OR52L1, CTSD, KBTBD13, and ATP2B4 present as missense mutations, while PRF1 and CTSD present as frameshift variants. Sanger sequencing confirmed the presence of the novel pathogenic variant PRF1 (c.124_128del) that has not been reported previously. More causal-effect or evidence-based studies will be required to elucidate the precise roles of these SNPs in the RP pathogenesis. Taken together, our findings may allow us to explore the risk variants based on the sequencing data and upgrade the existing variant annotation database in Taiwan. It may help detect specific eye diseases such as retinitis pigmentosa in East Asia.

An Update on Gene Therapy for Inherited Retinal Dystrophy: Experience in Leber Congenital Amaurosis Clinical Trials.

Inherited retinal dystrophies (IRDs) are a group of rare eye diseases caused by gene mutations that result in the degradation of cone and rod photoreceptors or the retinal pigment epithelium. Retinal degradation progress is often irreversible, with clinical manifestations including color or night blindness, peripheral visual defects and subsequent vision loss. Thus, gene therapies that restore functional retinal proteins by either replenishing unmutated genes or truncating mutated genes are needed. Coincidentally, the eye's accessibility and immune-privileged status along with major advances in gene identification and gene delivery systems heralded gene therapies for IRDs. Among these clinical trials, voretigene neparvovec-rzyl (Luxturna), an adeno-associated virus vector-based gene therapy drug, was approved by the FDA for treating patients with confirmed biallelic RPE65 mutation-associated Leber Congenital Amaurosis (LCA) in 2017. This review includes current IRD gene therapy clinical trials and further summarizes preclinical studies and therapeutic strategies for LCA, including adeno-associated virus-based gene augmentation therapy, 11-cis-retinal replacement, RNA-based antisense oligonucleotide therapy and CRISPR-Cas9 gene-editing therapy. Understanding the gene therapy development for LCA may accelerate and predict the potential hurdles of future therapeutics translation. It may also serve as the template for the research and development of treatment for other IRDs.

Comparing efficacy of charged-particle therapy with brachytherapy in treatment of uveal melanoma.

BACKGROUND: Uveal melanoma (UM) is the most common primary ocular tumour in adults. The most used eye-preserving treatments are charged-particle therapy (CPT) and brachytherapy. We performed a systematic review and meta-analysis to compare efficacies and complications of these two radiotherapies. METHODS: We searched EMBASE, PubMed, MEDLINE, and the Cochrane Library from January 2012 to December 2022. Two independent reviewers identified controlled studies comparing outcomes of CPT versus brachytherapy. Case series that utilize either treatment modality were also reviewed. RESULTS: One hundred fifty studies met the eligibility criteria, including 2 randomized control trials, 5 controlled cohort studies, and 143 case series studies. We found significant reduction in local recurrence rate among patients treated with CPT compared to brachytherapy (Odds ratio[OR] 0.38, 95% Confidence interval [CI] 0.24-0.60, p < 0.01). Analysis also showed a trend of increased risks of secondary glaucoma after CPT. No statistically significant differences were found in analyzing risks of mortality, enucleation, and cataract. CONCLUSIONS: Our study suggested no difference in mortality, enucleation rate and cataract formation rate comparing the two treatments. Lower local recurrence rate and possibly higher secondary glaucoma incidence was noted among patients treated with CPT. Nevertheless, the overall level of evidence is limited, and further high-quality studies are necessary to provide a more definitive conclusion.

Management of complications of sutureless intrascleral intraocular lens fixation.

PURPOSE: The purpose of the study was to report the complications of sutureless intrascleral (SIS) intraocular lens (IOL) fixation and its management. MATERIALS AND METHODS: A multicenter, retrospective, consecutive interventional case series of patients with intra or postoperative complications after SIS IOL fixation during the technical learning curve of vitreoretinal surgeons from three Taiwanese referral hospitals. The used surgical techniques were the Scharioth technique for intrascleral tunnel fixation, Yamane technique (double-needle scleral fixation), and modified Yamane technique (double-needle flanged haptic scleral fixation). The IOL models and surgical instruments used as well as each patient's ocular characteristics and complication management were recorded. RESULTS: Of the eight included patients, the complications of 3 (37.5%) and 5 (62.5%) were noted intraoperatively and postoperatively, respectively. Haptic-related complications, including haptic breakage, slippage, and haptic disinsertion, occurred in six eyes. Other complications included uveitis-glaucoma-hyphema syndrome, retinal detachment, and IOL tilt. For the two patients with haptic slippage, repositioning was achieved using a modified cow-hitch technique that resulted in favorable IOL centration and restored visual acuity. CONCLUSION: Most complications surgeons encountered during their early exposure to SIS IOL fixation were haptic related. Surgeons should be aware of such complications to prevent and manage them during surgery. Our modified cow-hitch technique could be used to reposition IOLs with unilateral haptic slippage.

Brolucizumab in recalcitrant neovascular age-related macular degeneration-real-world data in Chinese population.

This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.

Exome sequencing and genome-wide association analyses unveils the genetic predisposition in hydroxychloroquine retinopathy.

OBJECTIVES: To unveil the candidate susceptibility genes in chloroquine/hydroxychloroquine (CQ/HCQ) retinopathy using whole exome sequencing (WES) and genome-wide association study (GWAS). METHODS: Patients with a diagnosis of CQ/HCQ retinopathy based on the comprehensive demographic and ocular examination were included. The peripheral blood was extracted for WES and GWAS analyses. The Chinese Han Southern database from 1000 genomes was used as control group to compare the affected percentage. Multivariate logistic regression analysis adjusted for age, HCQ dose, duration and renal disease were used to analyze the correlation between genetic variants and visual outcome. A poor vision outcome was defined as visual acuity <6/12. An abnormal anatomical outcome was defined as disruption of ellipsoid zone in the fovea. RESULTS: Twenty-nine patients with an average age of 60.9 ± 13.4 years, treatment duration of 12.1 ± 6.2 years, daily dose of 8.5 ± 4.1 mg/kg, and the cumulative dose of 1637.5 ± 772.5 g, were genotyped. Several candidate genes associated with CQ/HCQ retinopathy were found, including RP1L1, RPGR and RPE65, with a difference of affected percentage over 50% in mutation between the case and control groups. New foci in CCDC66: rs56616026 (OR = 63.43, p = 1.63 × 10-8) and rs56616023 (OR = 104.7, p = 5.02 × 10-10) were identified significantly associated with HCQ retinopathy. Multivariate analysis revealed increased genetic variants were significantly associated with poor functional (OR = 1.600, p = 0.004) and structural outcome (OR = 1.318, p = 0.043). CONCLUSIONS: Several candidate susceptibility genes including RP1L1, RPGR, RPE65 and CCDC66 were identified to be associated with CQ/HCQ retinopathy. In addition to disease susceptibility, patients with increased genetic variants are more vulnerable to poor visual outcomes.

Retinal Microvascular Changes in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review, Meta-Analysis, and Meta-Regression.

Background: The remarkable increase in prevalence and significant morbidity of neurodegenerative diseases pose a tremendous burden for the health care system. Changes in retinal microvasculature metrics associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI) may provide opportunities for early diagnosis and intervention. However, the role of retinal vascular biomarkers remains controversial. We aim to perform a systematic review, meta-analysis and meta-regression to evaluate the comprehensive retinal microvasculature changes in patients with AD and MCI. Methods: We conducted a literature search on PubMed, MEDLINE, and EMBASE to identify studies published before May 2021 which assessed the measurements of optical coherence tomography angiography (OCTA) between AD, MCI with healthy control eyes, including foveal avascular zone (FAZ), vessel density (VD) of peripapillary, superficial and deep capillary plexus, and choroidal thickness using a random-effect model. We also performed meta-regression and subgroup analysis and assessed heterogeneity and publication bias to evaluate potential sources of bias. Results: Compared with control eyes, VD of superficial capillary plexus was significantly lower in AD [standardized mean difference (SMD): -0.48; 95% CI (-0.70 to -0.27); p = 0.04] and MCI eyes [SMD: -0.42; 95% CI (-0.81 to -0.03); p = 0.03], as well as reduced VD of deep capillary plexus [SMD: -1.19; 95% CI (-2.00 to -0.38]; p < 0.001], [SMD: -0.53; 95% CI (-0.85 to -0.22); p < 0.001]. FAZ was significantly enlarged in AD eyes [SMD: 0.54; 95% CI (0.09 to 0.99); p = 0.02]. The meta-regression analysis showed that the OCTA machine type and macular scan size significantly influenced the variation of VD and FAZ between AD and control eyes (p < 0.05). Conclusion: Our results highlight the potential of OCTA as a biomarker to detect early microvasculature deficits in AD and MCI. Notably, the macular scan size and different OCTA machine type could explain the heterogeneity observed in literatures. This information might be useful for future longitudinal study design to evaluate the role of OCTA in monitoring disease progression and treatment efficacy.

Comparison of Efficacy between Non-Steroidal Anti-Inflammatory Drugs and Anti-Vascular Endothelial Growth Factor in Preventing Macular Edema after Cataract Surgery in Diabetic Patients.

(1) Background: There is no consensus regarding the optimal strategy to prevent macular edema after cataract surgery in diabetic patients. The purpose of study is to compare the efficacy of topical nonsteroidal anti-inflammatory agents (NSAIDs) and intravitreal injections of anti-VEGFs for the prevention of macular edema after cataract surgery in diabetic patients without pre-existing macular edema. (2) Methods: A literature search of the MEDLINE, PUBMED, and EMBASE databases was conducted in July 2021. Studies involving either topical NSAIDs or intravitreal injections of anti-VEGF arms that reported either the occurrence of macular edema or changes in best corrected visual acuity (BCVA) were included. Weighted mean differences and risk ratios were calculated along with 95% confidence intervals. (3) Results: Intravitreal injection of anti-VEGFs provided short-term structural protection for one month in patients receiving cataract surgery, but the protective effect ceased to exist after three months. The structural protection of topical NSAIDs, however, can last for at least three months. Meanwhile, neither anti-VEGFs nor NSAIDs provided significant visual improvement. (4) Conclusions: Our study suggested that topical NSAIDs eye drops is an effective prevention strategy for macular edema after cataract surgery in diabetic patients.