Surgical management of a case of non-resolving bullous retinal detachment due to probable Vogt-Koyanagi-Harada syndrome.

A 45-year-old male with Vogt-Koyanagi-Harada (VKH) syndrome presented with vision loss in his right eye after discontinuing treatment during the COVID-19 pandemic. He was found to have bullous retinal detachment (RD) in the right eye and was started on subcutaneous adalimumab with oral corticosteroid following three doses of pulse corticosteroid. But when RD did not resolve after 4 months of treatment and ultrasound B scan showed bullous RD with retino-retinal adhesion, he was planned for surgical intervention. During surgery, there was retino-retinal adhesions due to long-standing "kissing exudative RD", causing non-settling exudative RD. Following surgery, the vision improved to 2/60, with attached retina. The patient has been under follow-up with us for the last one year now and developed no recurrence of RD till now. This case emphasises the significance of retinoretinal adhesion in long-standing bullous RD that does not respond to conventional aggressive medical therapy.

Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

Surgical outcomes in aggressive retinopathy of prematurity (AROP)-related retinal detachments.

Introduction: Aggressive retinopathy of prematurity (AROP) is a severe and progressive variant of retinopathy of prematurity (ROP) rapidly forming fibrous tissue extending from the disc toward the posterior lens surface progressing to Stage 5 disease without traversing the classical course that includes Stages 1 to 3. Since AROP behaves differently from type 1 ROP, this study was undertaken to evaluate the surgical outcome of AROP-related detachments. Methods: Retrospective analysis of data from electronic medical records of babies diagnosed with AROP-related detachments who underwent micro-incision vitrectomy surgery (MIVS) was included. The demographic data, details of primary intervention (laser and/or intravitreal bevacizumab), and surgery were noted. In a subset of patients, surgical intervention was planned early at the onset of fibrovascular tissue. Results: 43 eyes of 26 babies with median birth weight 1175 g and median gestational age of 29 weeks were analyzed. 42/43 eyes underwent primary intervention in form of laser and/or anti-VEGF injection before surgery. 41.8%, 25.5%, and 32.5% eyes progressed to stages 4A, 4B, and 5, respectively, requiring surgical intervention. 66% eyes underwent lensectomy and vitrectomy (LV), and 44% eyes underwent lens sparring vitrectomy (LSV). 58% eyes had attached macula. 44% eyes that had a relatively less vascular diseases had better anatomical outcome (P = 0.019). At final follow-up, 53.4% eyes followed or at least had light fixation, and 77.7% eyes undergoing LSV fixated and/or followed light compared to 33% for LV (P = 0.04). Conclusion: Challenges in AROP include rapid progression to advanced stages of ROP requiring close monitoring and multiple interventions. Surgeries for AROP have a favorable anatomical and functional outcome in 58% and 53%, respectively. Eyes undergoing lens sparing vitrectomy had better visual outcomes.

Age-Related Alterations of the Macular Choroid in Healthy Eyes Assessed by Swept-Source Optical Coherence Tomography Angiography.

OBJECTIVE: To analyze age-related changes in the choroid in healthy eyes using swept-source optical coherence tomography angiography (SS-OCTA). PATIENTS AND METHODS: This was a cross-sectional, prospective, observational study enrolling 222 eyes of 116 healthy participants. SS-OCTA images were captured using the PLEX Elite 9000 (Carl Zeiss Meditec) with a 6 x 6 mm pattern centered on the fovea. Subfoveal choroidal thickness (CT) and choroidal volume (CV) were generated automatically through manufacturer tools available in the Advanced Retinal Imaging (ARI) hub network. Choroidal vascularity index (CVI) and choriocapillaris flow deficits (CCFD) were computed using ImageJ. RESULTS: CV was found to be significantly higher in women than men. Overall, there was a significant positive correlation between CVI and CCFD, and a significant negative correlation between CT and CV with age. The relationship, however, was more complex, as a decade-wise analysis showed that CT and CV increased until the second decade, followed by a decrease until the sixth decade, and then an increase again in the seventh and eighth decades. CVI was highest in the seventh decade. In contrast, CCFD increased consistently with age and in all the Early Treatment of Diabetic Retinopathy Study (ETDRS) rings. CONCLUSION: The choroidal blood flow and its thickness reduces as the age advances. While the choroidal flow deficits show a consistent increase with age and the distance from the foveal center, the relationship of other parameters with age is more complex. Having a normative database from healthy subjects is imperative for understanding the changes taking place in diseased states. Choroidal parameters can show significant variations with age. These differences are not uniform or consistent with age, highlighting the importance of a normative reference database to assess the significance of choroidal alterations associated with disease. [Ophthalmic Surg Lasers Imaging Retina 2023;54:526-534.].

Mutation profile of Bardet-Biedl syndrome patients from India: Implicative role of multiallelic rare variants and oligogenic inheritance pattern.

Bardet-Biedl syndrome (BBS), a rare primary form of ciliopathy, with heterogeneous clinical and genetic presentation is characterized by rod cone dystrophy, obesity, polydactyly, urogenital abnormalities, and cognitive impairment. Here, we delineate the genetic profile in a cohort of 108 BBS patients from India by targeted gene sequencing-based approach for a panel of ciliopathy (including BBS) and other inherited retinal disease genes. We report here a higher frequency of BBS10 and BBS1 gene variations. A different spectrum of variations including a putatively novel gene TSPOAP1, for BBS was identified. Increased percentage frequency of digenic variants (36%) in the disease cohort, role of modifiers in familial cases are some of the salient observations in this work. This study appends the knowledge of BBS genetics pertaining to patients from India. We observed a different molecular epidemiology of BBS patients in this study cohort compared to other reports, which emphasizes the need for molecular testing in affected patients.

Next-generation sequencing--based genetic testing and phenotype correlation in retinitis pigmentosa patients from India.

Purpose: Inherited retinal dystrophies (IRD) are a heterogeneous group of retinal diseases leading to progressive loss of photoreceptors through apoptosis. Retinitis pigmentosa (RP) is considered the most common form of IRD. Panel-based testing in RP has proven effective in identifying the causative genetic mutations in 70% and 80% of the patients. This is a retrospective, observational, single-center study of 107 RP patients who had undergone next-generation sequencing-based targeted gene panel testing for IRD genes. These patients were inspected for common phenotypic features to arrive at meaningful genotype-phenotype correlation. Methods: Patients underwent complete ophthalmic examination, and blood was collected from the proband for DNA extraction after documenting the pedigree. Targeted Next Generation Sequencing (NGS) was done by panel-based testing for IRD genes followed by co-segregation analysis wherever applicable. Results: Of the 107 patients, 72 patients had pathogenic mutations. The mean age of onset of symptoms was 14 ± 12 years (range: 5-55). Mean (Best Corrected Visual Acuity) BCVA was 6/48 (0.9 logMAR) (range 0.0-3.0). At presentation, over one-third of eyes had BCVA worse than 6/60 (<1 logMAR). Phenotype analysis with the gene defects showed overlapping features, such as peripheral well-defined chorioretinal atrophic patches in patients with CERKL, PROM1, and RPE65 gene mutations and large macular lesions in patients with RDH12 and CRX gene mutations, respectively. Nummular or clump-like pigmentation was noted in CRB1, TTC8, PDE6A, and PDE6B. Conclusion: NGS-based genetic testing can help clinicians to diagnose RP more accurately, and phenotypic correlations can also help in better patient counselling with respect to prognosis and guidance regarding ongoing newer gene-based therapies.

Fractal analysis of the macular region in healthy eyes using swept-source optical coherence tomography angiography.

PURPOSE: This cross-sectional observational study evaluated the relationship between retinal vascular fractal dimension (FD) and age, as well as other vascular parameters in healthy eyes using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: The study cohort consisted of 222 eyes of 116 healthy participants with no ocular or systemic disease. SS-OCTA images were captured and analyzed using the Plex Elite 9000 and software tools available in the advanced retinal imaging (ARI) network hub. The retinal vascular layers were defined by the instrument's automatic retinal layer segmentation. The fractal analysis was performed on the superficial capillary plexus (SCP), deep capillary plexus (DCP), and the whole retina. Grayscale OCTA images were standardized and binarized using ImageJ and fractal box-counting analyses were performed using Fractalyse software. Pearson's correlation was used to analyze the correlation between FD and retinal vascular parameters. RESULTS: The results showed that FD values were significantly higher in the 6 mm ring and the whole 6 × 6 scan region when compared to the 1 mm ETDRS central subfield. The correlation between age and FD was weak with a significant positive correlation between age and FD of the SCP in the 6 mm ring and between age and FD of the DCP in the 1 mm ring. Overall, differences in FD values in these healthy eyes were extremely small regardless of age or macular location. CONCLUSION: FD values in normal eyes show little variation with age and are relatively stable across the macula. This suggests that FD values may not need adjustment for age or location when evaluated in the context of retinal disease.

Polypoidal Choroidal Vasculopathy: An Update on Diagnosis and Treatment.

Polypoidal choroidal vasculopathy (PCV) is a vascular disease of the choroid that leads to hemorrhagic and exudative macular degeneration. It may cause significant vision loss and thus affect the quality-of-life and psychological well-being. Non-invasive, non-ICGA-based OCT criteria have shown reliable results to plan adjunct photodynamic therapy (PDT) treatment, with the complete and consistent coverage of polypoidal lesions (PL) and branching neovascular network (BNN). The safety and efficacy of anti-vascular endothelial growth factor (anti-VEGF) monotherapy and its combination with verteporfin PDT have been established. However, treatment is still challenging due to frequent follow-ups, non-availability of PDT, and need for multiple anti-VEGF injection visits that increase the treatment burden and lead to patients being lost to follow-up. Effective treatments that prolong intervals between injections while maintaining vision and anatomical gains remain a critical unmet need. Longer acting molecules, like brolucizumab, have shown non-inferiority in BCVA gains and superior anatomical outcomes compared to other anti-VEGF agents. Newer therapies in the pipeline to enhance the efficacy and longevity of treatment include Faricimab and a port delivery system (PDS). This review summarizes the most recent diagnostic and treatment approaches in PCV to offer better treatment avenues.

COMBINED HAMARTOMA OF THE RETINA AND RETINAL PIGMENT EPITHELIUM AT PEDIATRIC AGE: Surgical Versus Conservative Approach.

PURPOSE: To report outcomes of pediatric patients with combined hamartoma of the retina and the retina pigment epithelium followed up conservatively or after pars plana vitrectomy. METHODS: This retrospective multicenter study included 62 eyes of 59 pediatric patients with combined hamartoma of the retina and the retina pigment epithelium from 13 different international centers with an average age of 7.7 ± 4.7 (0.3-17) years at the time of the diagnosis and having undergone pars plana vitrectomy or followed conservatively. At baseline and each visit, visual acuity values, optical coherence tomography for features and central foveal thickness, and tumor location were noted. Lesions were called as Zone 1, if it involves the macular and peripapillary areas, and the others were called as Zone 2 lesions. RESULTS: Twenty-one eyes of 20 patients in the intervention group and 41 eyes of 39 patients in the conservative group were followed for a mean of 36.2 ± 40.4 (6-182) months. Best-corrected visual acuity improved in 11 (68.8%) of 16 eyes in the intervention group and 4 (12.9%) of 31 eyes in the conservative group ( P < 0.001). The mean central foveal thickness decreased from 602.0 ± 164.9 µ m to 451.2 ± 184.3 µ m in the intervention group, while it increased from 709.5 ± 344.2 µ m to 791.0 ± 452.1 µ m in Zone 1 eyes of the conservative group. Posterior location of tumor, irregular configuration of the foveal contour and ellipsoid Zone defect in optical coherence tomography, subretinal exudate and prominent vascular tortuosity were associated with poor visual acuity. CONCLUSION: Vitreoretinal surgery is safe and effective in improving vision and reducing retinal distortion in Zone 1 combined hamartoma of the retina and the retina pigment epithelium in children.

Association of HERPUD1 genetic variant rs2217332 with age-related macular degeneration and polypoidal choroidal vasculopathy in an Indian cohort.

PURPOSE: Age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are sister diseases and have several similar clinical features and still have few genetic differences. The association of HERPUD1 (homocysteine inducible ER protein with ubiquitin like domain 1) gene variant rs2217332 with PCV is known; however, such association with AMD has not been reported in the Indian population. We analyzed the association of rs2217332 with PCV and AMD to identify the preferential association of this variant with these diseases. METHODS: This is a population-based case-control study consisting of 422 patients (129 AMD cases; 101 PCV cases, 192 healthy controls) recruited from the vitreoretinal clinic Sankara Nethralaya. The sample size for the study was calculated using appropriate power calculation methods. Genotype was determined using PCR-based Sanger sequencing. The SPSS V23.0 statistical package tool was used to calculate chi-square and ROC to determine the association of rs2217332 with control, AMD, and PCV. RESULTS: Here, we report for the first time the association of this genetic variant (rs2217332) with AMD and PCV in the Indian population. The case-control study shows a significant association of this SNP with PCV (P value = 0.002); however, this variant is not significantly associated with AMD (P value = 0.602). Comparison between AMD (as control) and PCV (as case) also showed significant association of the SNP with PCV (P value = 0.02). Minor allele A conferred to increase the risk of PCV. CONCLUSIONS: The study concludes that the genetic variant rs2217332 in HERPUD1 gene is highly significantly associated with PCV and not with AMD in Indian populations.

Optical Coherence Tomography-Based Choroidal Structural Analysis and Vascularity Index in Best Vitelliform Macular Dystrophy.

INTRODUCTION: This study investigated choroidal structural changes on optical coherence tomography (OCT) using choroidal vascularity index (CVI) and choroidal thickness (CT) in patients with Best vitelliform macular dystrophy (BVMD). METHODS: This retrospective case control study included 78 patients with BVMD of different clinical stages and 242 age- and gender-matched healthy controls. Subfoveal OCT scans were analysed. Total choroidal area (TCA), luminal area (LA) and CT were measured after image segmentation and binarization. CVI, a novel marker for choroidal angioarchitecture, was defined as the ratio of LA to TCA. CVI and CT were compared between BVMD and control group, as well as among the BVMD subgroups. RESULTS: Mean CVI was lower in eyes with BVMD (65.0 ± 3.5%) compared to that in control eyes (67.5 ± 3.9%) and this was statistically significant (p < 0.0001). There was no significant difference in subfoveal CT between BVMD (302.88 ± 81.68 µm) and control (309.31 ± 65.46 µm) eyes (p = 0.4799). In the subgroup analysis, all stages of BVMD showed lower CVI compared to control while SFCT remained similar. Within the BVMD subgroups, CVI and subfoveal CT did not differ significantly and both were not shown to be associated with visual acuity. CONCLUSION: Decreased CVI was shown in eyes with BVMD compared to control eyes, while no significant difference in subfoveal CT was seen. CVI may be helpful in the understanding of choroidal pathology in BVMD.

Choriocapillaris flow deficits in polypoidal choroidal vasculopathy using swept source optical coherence tomography angiography.

Purpose: To evaluate the choriocapillaris flow deficits (CCFD) on swept-source optical coherence tomography angiography (SS-OCTA) in eyes with unilateral polypoidal choroidal vasculopathy (PCV), fellow unaffected eyes, and to compare them with age-matched healthy controls. Methods: This study was a cross-sectional study which included treatment-naïve eyes with unilateral PCV (group 1), fellow unaffected eyes of patients with PCV (group 2), and normal eyes (group 3). Using the SS-OCTA, the Choriocapillaris (CC) slab was segmented from the structural optical coherence tomography (OCT) and the corresponding flow map was multiplied after signal compensation. The resultant image was evaluated for CCFD in equidistant squares measuring 1 × 1 mm, 1.5 × 1.5 mm, 2 × 2 mm, 2.5 × 2.5 mm, 3 × 3 mm, and 6 × 6 mm centered on the fovea. Results: The percentage of flow deficits were significantly increased (one-way ANOVA, P = 0.003 and P = 0.049) in the eyes with PCV as compared to the fellow eyes, and age-matched healthy controls. In the multiple pairwise comparison using post hoc Bonferroni, CCFD of 1 mm in group 1 and 2 (P = 0.019), group 1 and 3 (P = 0.003), and CCFD of 1.5 mm in group 1 and 3 (P = 0.044) were statistically significant. Correlation analysis showed no significant correlation between CCFD, age, Best corrected visual acuity (BCVA), foveal thickness (FT), and subfoveal choroidal thickness (SFCT) in our study. Linear regression analysis showed that the CCFD was negatively correlated with the distance from the foveal center in group 1 (ß = -0.613, P = 0.046). Conclusion: Eyes with PCV demonstrated a significant flow impairment in the choriocapillaris layer as compared to the fellow unaffected eyes and age-matched healthy eyes.

Age-related assessment of foveal avascular zone and surrounding capillary networks with swept source optical coherence tomography angiography in healthy eyes.

AIM: To assess the macular capillary networks and foveal avascular zone (FAZ) with swept-source optical coherence tomography angiography in healthy eyes. METHODS: This cross-sectional, prospective, observational study enrolled 222 eyes of 116 healthy participants with no ocular or systemic disease. SS-OCTA images were captured using the PLEX Elite 9000 (Carl Zeiss Meditec Inc., Dublin, CA, USA) with a 6 × 6 mm pattern centered on the foveal center. Vessel length density (VLD), perfusion density (PD), and FAZ parameters were analyzed using the manufacturer's automated software. RESULTS: A significant negative correlation was observed between age and average VLD in the superficial plexus, and average PD in both the superficial plexus and the whole retina. A significant positive correlation between age and foveal avascular zone perimeter and area was also noted. Age-wise comparisons showed a trend for an increase in VLD and PD until 40 years of age, with a subsequent decrease in the older age in the macular region. The central subfield showed a decrease in the vessel density measurements in the 21-40 age group. FAZ area and perimeter were the mirror inverse of the central subfield vessel density measurements with a numerically greater area and perimeter in the 21-40 age group compared to the 0-20 and 41-60 age groups. FAZ circularity was significantly reduced after 40 years of age. CONCLUSION: Age-related changes in the vessel density and FAZ parameters in the healthy macula are complex and vary with the macular location. These results carry significance when interpreting the data from diseased eyes.

Structural and functional changes among diabetics with no diabetic retinopathy and mild non-proliferative diabetic retinopathy using swept-source optical coherence tomography angiography and photopic negative response.

PURPOSE: To assess the structural and functional changes among diabetics with no diabetic retinopathy (NDR) and mild non-proliferative diabetic retinopathy (NPDR) using swept-source optical coherence tomography angiography (SSOCTA) and photopic negative response (PhNR) and to find the earliest changes. METHODS: This was a prospective, cross-sectional, case-control study. Participants with minimum 5 years of diabetes mellitus (DM) were recruited and classified as NDR and mild NPDR based on fundus findings. Age-matched normals with nil ocular pathology were considered as controls. SSOCTA scan acquisition (6*6 mm angiography), followed by full field photopic electroretinography (FFERG) and red on blue PhNR (R/B PhNR) were done with complete pupillary dilatation. RESULTS: A total of 88 participants were included with 35 controls, 39 NDR and 14 mild NPDR subjects. Vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of mild NPDR were significantly reduced compared to the controls (17.12 ± 2.65 mm-1 vs. 18.75 ± 0.90 mm-1, p = 0.025 and 7.96 ± 3.92 mm-1 vs. 11.83 ± 3.05 mm-1, p = 0.001 respectively). None of the parameters of controls had significant difference compared to NDR group (p > 0.05). The amplitudes of white on white (W/W) a-wave, W/W b-wave, red on blue (R/B) PhNR baseline to trough (BT) and R/B PhNR peak to trough in controls were significantly high compared to NDR and mild NPDR. Amplitude of R/B PhNR BT had the maximum area under the curve of 75.9% with a sensitivity and specificity of 94.3and 77.4%, respectively. CONCLUSION: A significant decrease in functional changes as measured by ERG especially PhNR, is seen even among the NDR group compared to controls unlike SSOCTA parameters that measures very early vascular structural changes. PhNR is a sensitive test to identify early preclinical changes in DR when microvascular structural changes as determined by SSOCTA are normal.

Clinical explainable differential diagnosis of polypoidal choroidal vasculopathy and age-related macular degeneration using deep learning.

BACKGROUND: This study aims to achieve an automatic differential diagnosis between two types of retinal pathologies with similar pathological features - Polypoidal choroidal vasculopathy (PCV) and wet age-related macular degeneration (AMD) from volumetric optical coherence tomography (OCT) images, and identify clinically-relevant pathological features, using an explainable deep-learning-based framework. METHODS: This is a retrospective study with data from a cross-sectional cohort. The OCT volume of 73 eyes from 59 patients was included in this study. Disease differentiation was achieved through single-B-scan-based classification followed by a volumetric probability prediction aggregation step. We compared different labeling strategies with and without identifying pathological B-scans within each OCT volume. Clinical interpretability was achieved through normalized aggregation of B-scan-based saliency maps followed by maximum-intensity-projection onto the en face plane. We derived the PCV score from the proposed differential diagnosis framework with different labeling strategies. The en face projection of saliency map was validated with the pathologies identified in Indocyanine green angiography (ICGA). RESULTS: Model trained with both labeling strategies achieved similar level differentiation power (>90%), with good correspondence between pathological features detected from the projected en face saliency map and ICGA. CONCLUSIONS: This study demonstrated the potential clinical application of non-invasive differential diagnosis using AI-driven OCT-based analysis, with minimal requirement of labeling efforts, along with clinical explainability achieved through automatically detected disease-related pathologies.