Understanding the relationship between pachychoroid spectrum disorders and retinitis pigmentosa: A review of the evidence.

This study aims to investigate the relationship between pachychoroid spectrum disorders and retinitis pigmentosa (RP) or rod-cone dystrophy through a comprehensive literature review. The purpose is to explore the association between these disorders, understand their underlying mechanisms, and summarize the existing hypotheses and opinions. A thorough review of the literature was conducted using PubMed, focusing on articles related to central serous chorioretinopathy (CSC), RP, pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy, focal choroidal excavation, peripapillary pachychoroid neovasculopathy, and peripheral exudative hemorrhagic chorioretinopathy. Relevant studies were selected for a detailed narrative review and analysis. Several studies have reported the coexistence of CSC and RP, indicating a potential association between the two conditions. The dysfunction of the retinal pigment epithelium is proposed as a common factor. Choroidal thinning is observed in RP, but conflicting results exist regarding choroidal thickness (CT). While some studies support choroidal thinning in RP, others suggest preserved or increased thickness. Additionally, cases of pachychoroid neovasculopathy and polypoidal choroidal vasculopathy in RP have been reported, suggesting an overlap between these conditions. The literature suggests conflicting reports on CT changes in RP. Future research should focus on large-scale studies using comprehensive imaging techniques, genetic analysis, and long-term follow-up to uncover the underlying mechanisms and determine the prevalence of pachychoroid spectrum disorders in RP patients.

Retinopathy of prematurity in triplets - Indian twin city ROP study report number 12.

PURPOSE: To evaluate the incidence and severity of retinopathy of prematurity (ROP) amongst surviving triplets. METHODS: Records of preterm babies born to mothers with triplet pregnancies were retrieved from our Indian twin city ROP study database between 1 Jan 2000 and 31 Dec 2020 and analyzed. RESULTS: 253 surviving triplet babies born to 108 mothers were evaluated. 48 out of 108 (44%) mothers received treatment for infertility. Data was available and analyzed for 242 babies (484 eyes). Mean gestational age was 31.76 ± 3.74 weeks (26- 38 weeks). The mean birth weight was 1.44 ± 0.37 kg (0.57-2.76 kg). At the first screening, incomplete vascularization was noted in 67% (131 babies;322 eyes) of which ROP was diagnosed in 14% (28 babies; 56 eyes). Among them, only 18 babies (53%) were the smallest birth weight babies in each of the triplet sets. Treatment with laser or bevacizumab was performed in 14 babies (5.8%), one eye of one baby additionally needed vitreoretinal surgical intervention. Good anatomical outcomes in terms of regression of ROP without sequelae were achieved in all babies. CONCLUSION: The present study reveals low incidence and favorable outcomes of ROP in triplet pregnancies in a large cohort of babies from a middle-income country. Our cohort did not show any difference in the treatment-requiring ROP among the larger or smaller birth weight babies of the same gestational age. In multiple pregnancies, gestational age remains a critical factor for ROP development; however, this does not necessitate modifying screening or treatment criteria in such triplet pregnancies.

Generation of two induced pluripotent stem cell lines (LVPEIi004-A and LVPEIi005-A) from probands with Leber Congenital Amaurosis 2 (LCA2) and harboring mutations in RPE65.

Leber Congenital Amaurosis 2 is an early onset retinal dystrophy that occurs due to mutation in RPE65 gene. Here, we report the generation of two patient specific induced pluripotent stem cell lines harboring nonsense mutations in exon 7 (c.646A > T) and exon 9 (c.992G > A) of RPE65 gene, respectively, which leads to premature translational termination and formation of defective protein. These lines were generated by the reprogramming of human dermal fibroblast cells using integration-free, episomal constructs expressing stemness genes. The stable lines maintained a normal karyotype, expressed the key stemness factors, underwent trilineage differentiation, and maintained their genetic identity and genomic integrity.

Generation of two induced pluripotent stem cell lines (LVPEIi007-B, LVPEIi008-B) from patients harboring homozygous mutation in ABCA4 (c.6088C>T) using non-integrative Sendai virus-based approach.

Mutations in ABCA4 gene leads to the most common form of an inherited retinal disease namely, the Stargardt disease, type 1. Here, we report the generation of two different patient-specific induced pluripotent stem cell lines (LVPEIi007-B and LVPEIi008-B), carrying an identical homozygous mutation, (c.6088C>T) within the exon 44 of ABCA4 gene. These lines were generated by the reprogramming of patient-specific dermal fibroblasts, using the integration-free, Sendai viral vectors. Both lines were stably expanded and expressed the stemness and pluripotency markers, differentiated into cell types of all three germ layers, and maintained a normal karyotype.

Generation of Leber congenital amaurosis, type 12 patient-specific induced pluripotent stem cell line (LVPEIi006-A), harboring a homozygous mutation in RD3.

Leber congenital amaurosis (LCA) is a congenital, early onset, autosomal recessive inherited retinal disease (IRD). This report describes an LCA12 patient-specific iPSC line (LVPEIi006-A), generated by the reprogramming of dermal fibroblasts using integration-free episomal plasmids.This disease-specific iPSC model carries a homozygous point mutation in RD3, within the donor splice site at the end of exon 2 (c.296 + 1G > A). The stable line at passage 15 has displayed a normal colony morphology, expressed multiple stemness and pluripotency markers, lost all transgenes, differentiated into cell types of all three germ layers, and maintained a normal karyotype.

RPE65 mutations in Leber congenital amaurosis, early-onset severe retinal dystrophy, and retinitis pigmentosa from a tertiary eye care center in India.

INTRODUCTION: Mutations in the retinal pigment epithelial 65 kilodalton protein (RPE65) gene are associated with various inherited retinal diseases (IRDs), including Leber congenital amaurosis (LCA), early-onset severe retinal dystrophy (EOSRD), and retinitis pigmentosa (RP). We screened for mutations in RPE65 in a series of Indian patients with these IRDs to determine the frequency/types of mutations and to describe the associated phenotypes. MATERIALS AND METHODS: Diagnosis of LCA, EOSRD, and RP was made by standard and pre-defined criteria. Patients were evaluated by clinical, retinal imaging, and electrophysiological parameters. Genomic DNA from patients and available family members were used for identifying mutations by direct Sanger sequencing of the RPE65 gene or targeted NGS gene panel for IRDs covering 260+ genes. Variations detected were tested in healthy control populations and for co-segregation with the disease in available family members. RESULTS: Mutations were found in eight patients, out of 220 total cases screened, all homozygous for the respective mutant alleles. Seven patients had mutations leading to premature termination codons and one patient had a missense change. The onset of visual loss ranged from birth to <2 years of life. At presentation, RPE mottling in the background retina was present in all cases with macular involvement in five cases with or without vascular attenuation and optic disc pallor. CONCLUSION: RPE65 mutations in this series were found in 3.6% of cases associated with severe, early-onset disease, with consistent RPE mottling and variable manifestations with regard to the extent of disc pallor, arteriolar attenuation, and appearance of the macula.

Outcome of eyes treated for Retinopathy of Prematurity in Posterior Zone I: An Eastern India study.

PURPOSE: To analyze the outcomes of eyes treated for retinopathy of prematurity (ROP) in posterior Zone I. METHODS: In a part retrospective (nine years) and part prospective (one year) interventional study, we analyzed eyes treated for ROP in posterior Zone I with a minimum follow-up for 6 months. RESULTS: The study included 109 eyes of 56 infants; mean gestational age and birth weights were 29.3 (±2.1) weeks and 1112.5 (±381.9) grams, respectively. The treatment included intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) as the initial treatment modality in 101 eyes (92.6%), either alone (27 eyes) or combined with laser or vitreous surgery (73 eyes). Laser was the initial treatment modality in 8 eyes, either alone-(n=3) or in combination with surgery (n=5). With anti-VEGF alone, 30.68% (n=27 eyes) responded favorably, and the remaining 69.32% (n=59) eyes needed re-treatment (laser in the majority). At the final follow-up, 89.9 % (out of 109) of eyes did well anatomically. Good outcome was significantly linked to no detachment at presentation (p<0.0001) and the presence of well-defined central vascular trunks (p=0.001). CONCLUSIONS: Treating the eyes before retinal detachment with bevacizumab followed by laser (and surgery, if needed) results in a favorable outcome in babies with posterior zone 1 ROP.

Outcome of real-time telescreening for retinopathy of prematurity using videoconferencing in a community setting in Eastern India.

PURPOSE: To evaluate the feasibility and outcome of a real-time retinopathy of prematurity (ROP) telescreening strategy using videoconferencing in a community setting in India. METHOD: In a prospective study, trained allied ophthalmic personnel obtained the fundus images in the presence of the parents and local childcare providers. Analysis of images and parental counseling were done in real time by an ROP specialist located at a tertiary center using videoconferencing software. A subset of babies was also examined using bedside indirect ophthalmoscopy by an ROP care-trained ophthalmologist. The data were analyzed using descriptive statistics, sensitivity, specificity, positive and negative predictive values, and correlation coefficient. RESULTS: Over 9 months, we examined 576 babies (1152 eyes) in six rural districts of India. The parents accepted the model as they recognized that a remotely located specialist was evaluating all images in real time. The strategy saved the travel time for ROP specialists by 477 h (47.7 working days) and for parents (47,406 h or 1975.25 days), along with the associated travel cost. In a subgroup analysis (100 babies, 200 eyes), the technology had a high sensitivity (97.2%) and negative predictivity value (92.7%). It showed substantial agreement (k = 0.708) with the bedside indirect ophthalmoscopy by ROP specialists with respect to the detection of treatment warranting ROP. Also, the strategy helped train the participants. CONCLUSION: Real-time ROP telescreening using videoconferencing is sensitive enough to detect treatment warranting ROPs and saves skilled workforce and time. The real-time audiovisual connection allows optimal supervision of imaging, provides excellent training opportunities, and connects ophthalmologists directly with the parents.

Clinico-Microbiological Correlation in Salmonella Endophthalmitis: Case Series and Review of Literature.

PURPOSE: To report two rare cases of Salmonella endogenous endophthalmitis in an immunocompromised premature baby and an immunocompetent adult and do a brief literature review of related cases. Diagnosis in both cases was confirmed only after the pathogen grew from ocular samples, in the absence of clear signs of enteric fever. METHODS: Retrospective analysis of medical and microbiology records. RESULTS: Both of our cases of Salmonella endophthalmitis had poor visual outcome, despite timely and aggressive management and irrespective of immune status of the patient. Salmonella infection being a rare cause of endophthalmitis was not initially suspected as the adult had minimal systemic symptoms 2 weeks before presentation, while the preterm baby was still on milk feeds. These were just two microbiologically confirmed cases of Salmonella endophthalmitis at our institute over the past 10 years, though enteric fever due to Salmonella species is endemic in Asian countries. CONCLUSIONS: Salmonella endophthalmitis, though rare, leads to poor visual outcomes despite early recognition and aggressive management and may be confused with other infections or non-infectious entities such as necrotizing retinoblastoma in babies, in the absence of clear systemic signs of the disease.

Outcomes of vitreoretinal surgery in eyes with retinitis pigmentosa without retinal detachment.

PURPOSE: Outcomes of retinal detachment (RD) have been discussed in detail in many reports of patients with retinitis pigmentosa (RP). This study tries to understand the outcomes of vitreoretinal (VR) surgery for indications other than RD in the eyes with RP. METHODS: This is a retrospective study that includes clinical data from January 2013 to December 2021. Patients with RP who were treated with a VR surgical intervention were included in the study. The primary outcome of the study was to assess the changes in best-corrected visual acuity. RESULTS: Forty-four eyes of 40 patients with RP were included in the study. Nearly half of the eyes (43%, 19/44) presented from 1 month to 1 year after the onset of diminished vision, with or without floaters. The mean ± standard deviation (SD) best-corrected visual acuity (BCVA) at presentation was 1.30 ± 0.79 logMAR (20/400 ± 20/125). The major surgical indications were vitreous opacities (43.2%, 19/44) and subluxated/dislocated cataractous lenses (25%, 11/44). The median follow-up duration was 8 months (interquartile range (IQR): 1.5-27). Approximately 77% (34/44) of the eyes had improvement in vision. The mean postoperative BCVA at the last follow-up was 0.95 ± 0.73 logMAR (p-value: 0.03). CONCLUSIONS: Most eyes with RP recovered well after VR surgical interventions, with short-term improvements in visual acuity. It may be crucial to address the vitreous opacities and membranes as they hinder the residual central island of vision in RP. However, appropriate counselling is required regarding the progressive nature of retinal neuronal degeneration.

Gene Therapy for Inherited Retinal Diseases: From Laboratory Bench to Patient Bedside and Beyond.

This comprehensive review provides a thorough examination of inherited retinal diseases (IRDs), encompassing their classification, genetic underpinnings, and the promising landscape of gene therapy trials. IRDs, a diverse group of genetic conditions causing vision loss through photoreceptor cell death, are explored through various angles, including inheritance patterns, gene involvement, and associated systemic disorders. The focal point is gene therapy, which offers hope for halting or even reversing the progression of IRDs. The review highlights ongoing clinical trials spanning retinal cell replacement, neuroprotection, pharmacological interventions, and optogenetics. While these therapies hold tremendous potential, they face challenges like timing optimization, standardized assessment criteria, inflammation management, vector refinement, and raising awareness among vision scientists. Additionally, translating gene therapy success into widespread adoption and addressing cost-effectiveness are crucial challenges to address. Continued research and clinical trials are essential to fully harness gene therapy's potential in treating IRDs and enhancing the lives of affected individuals.

Evaluation of optical coherence tomography biomarkers to differentiate favourable and unfavourable responders to intravitreal anti-vascular endothelial growth factor treatment in retinopathy of prematurity.

OBJECTIVE: Evaluation of optical coherence tomography biomarkers in predicting treatment response to intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) Bevacizumab, in aggressive retinopathy of prematurity (A-ROP). METHODS: Non-contact ultra-widefield (NC-UWF) fundus imaging with integrated UWF guided swept source Optical coherence tomography (SS-OCT) was performed prospectively in preterm babies before and after intravitreal anti-VEGF (Bevacizumab) monotherapy. OCT biomarkers were analysed in eyes that reached complete vascularization versus others. RESULTS: Eyes with retinal vessels reaching near ora serrata were labelled as regressed ROP and vascularised retina (Group1). Eyes with reactivation of ROP needing laser or vitreoretinal surgery or eyes with peripheral avascular retina (PAR) at 16th week post-injection were considered as Group 2. Pre-injection baseline OCT showed a hyperreflectivity of inner retinal layers in 12 out of 46 eyes in Group 1 versus 30 out of 34 eyes in Group 2 (p value 0.002). None of the eyes in Group 1 showed choroidal thinning at posterior pole as compared to 14 out of 34 eyes in Group 2 (p value 0.001). Intraretinal hypo reflective Cystic changes at fovea were seen in 16 out of 46 eyes in Group 1 and 2 out of 34 eyes in Group 2 (p value 0.012). CONCLUSION: Pre-injection swept source OCT biomarkers could predict the treatment outcomes of anti-VEGF (Bevacizumab) monotherapy in A-ROP eyes. Hyperreflectivity of inner retinal layers and choroidal thinning had poorer and unpredictable response to anti-VEGF injection whereas, cystic changes at fovea predicted favourable response.

Characteristics of posterior zone I retinopathy of prematurity.

OBJECTIVE: To report the demographic profile and clinical characteristics of retinopathy of prematurity (ROP) in posterior Zone I. METHODS: In a partly retrospective (ten years) and partly prospective (one year) study, we analysed the demographic profile and clinical characteristics of babies with ROP in posterior Zone I. RESULTS: The study included 130 eyes of 67 infants with a mean gestational age and birth weight of 29.3 (±2.2) weeks and 1217.3 (±381.9) grams, respectively. All babies had received unblended oxygen. In 47 of 51 (91.1%) babies, the weekly weight gain was <100 g (details were not available in 16 babies). The ROP subtypes included aggressive, threshold, hybrid, stage 4, and atypical types in 78 (60%), 20 (15.4%), 11 (8.5%), 15 (11.5%), and 6 (4.6%) eyes, respectively. Fibrovascular proliferation, when present, was prominent nasally, occasionally overriding the disc margin. Extensive arteriovenous tortuosity was more prominent than vascular dilatation. Atypical observations included bleb-like detachment (6 eyes; 4.6%) and candle wax-like preretinal deposits (23 eyes; 17.7%). CONCLUSIONS: Retinopathy of Prematurity in posterior Zone I in this cohort was strongly associated with 100% unblended oxygen supplementation, poor weight gain, and multiple systemic co-morbidities. ROP in posterior zone 1 has a distinct profile with several atypical characteristics different from ROP in other zones.

Color fundus imaging in retinopathy of prematurity screening: Present and future.

Advent of pediatric handheld fundus cameras like RetCam, 3netra Forus, and Phoenix ICON pediatric retinal camera has aided in effective screening of retinopathy of prematurity (ROP), especially in countries with limited number of trained specialists. Recent advent of various smartphone-based cameras has made pediatric fundus photography furthermore affordable and portable. Future advances like ultra-wide field fundus cameras, trans-pars-planar illumination pediatric fundus camera, artificial intelligence, deep learning algorithm, and handheld SS-OCTA can help in more accurate imaging and documentation. This article summarizes the features of existing and upcoming imaging modalities in detail, including their features, advantages, challenges, and effectiveness, which can help in implementation of telescreening as a standard screening protocol for ROP across developing as well as developed countries.

Electronic medical records driven big data analytics in retinal diseases, report number 1: non-oncological retinal diseases in children and adolescents in India.

PURPOSE: To describe the spectrum and demographic distribution of non-oncological retinal diseases in children and adolescents presenting to a multi-tier ophthalmic hospital network in India. METHODS: This is a cross-sectional hospital-based retrospective study over nine years (March 2011-March 2020) from a pyramidal eye care network in India. The analysis included 477,954 new patients (0-21 years), collected from an International Classification of Diseases (ICD) coded electronic medical record (EMR) system. Patients with a clinical diagnosis of retinal disease (non-oncological) in at least one eye were included. Age-wise distribution of these diseases in children and adolescents was analysed. RESULTS: In the study, 8.44% (n = 40,341) of new patients were diagnosed with non-oncological retinal pathology in at least one eye. The age group-specific distribution of retinal diseases was 47.4%, 11. 8%, 5.9%, 5.9%, 6.4%, 7.6% in infants (< 1 year), toddlers (1-2 years), early childhood (3-5 years), middle childhood (6-11 years), early adolescents (12-18 years) and late adolescents (18-21 years), respectively. 60% were male, and 70% had bilateral disease. The mean age was 9.46 ± 7.52 years. The common retinal disorders were retinopathy of prematurity (ROP, 30.5%), retinal dystrophy (19.5%; most commonly, retinitis pigmentosa), and retinal detachment (16.4%). Four-fifth of the eyes had moderate to severe visual impairment. Nearly one-sixth of patients needed low vision and rehabilitative services, and about 1 in 10 patients required surgical intervention (n = 5960, 8.6%). CONCLUSION AND RELEVANCE: About 1 in 10 children and adolescents seeking eye care in our cohort had non-oncological retinal diseases; the common ones were ROP (in infants) and retinitis pigmentosa (in adolescents). This information would help future strategic planning of eye health care in the institution in pediatric and adolescent age groups.

Visual impairment and blindness due to retinitis pigmentosa in India: 15-year follow-up of the Andhra Pradesh Eye Disease Study cohort.

Purpose: To assess the incidence, visual impairment, and blindness due to retinitis pigmentosa (RP) in a rural southern Indian cohort. Methods: This is a population-based longitudinal cohort study of participants with RP from the Andhra Pradesh Eye Disease Study (APEDS) cohorts I and III, respectively. The study included participants with RP of APEDS I who were followed until APEDS III. Their demographic data along with ocular features, fundus photographs, and visual fields (Humphrey) were collected. Descriptive statistics using mean ± standard deviation with interquartile range (IQR) were calculated. The main outcome measures were RP incidence, visual impairment, and blindness as per the World Health Organization (WHO) definitions. Results: At baseline (APEDS I), 7771 participants residing in three rural areas were examined. There were nine participants with RP with a mean age at baseline of 47.33 ± 10.89 years (IQR: 39-55). There was a male preponderance (6:3), and the mean best-corrected visual acuity (BCVA) of 18 eyes from nine participants with RP was 1.2 ± 0.72 logarithm of minimum angle of resolution (logMAR; IQR: 0.7-1.6). Over a mean follow-up duration of 15 years, 5395/7771 (69.4%) were re-examined, which included seven RP participants from APEDS 1. Additionally, two new participants with RP were identified; so, the overall incidence was 370/ million in 15 years (24.7/million per year). The mean BCVA of 14 eyes of seven participants with RP who were re-examined in APEDS III was 2.17 ± 0.56 logMAR (IQR: 1.8-2.6), and five of these seven participants with RP developed incident blindness during the follow-up period. Conclusion: RP is a prevalent disease in southern India that warrants appropriate strategies to prevent this condition.

Intravitreal Clindamycin as an Adjuvant Therapy in Congenital Toxoplasma Retinochoroiditis in a Neonate - A Case Report.

PURPOSE: To report a case of active retinochoroiditis in a neonate treated with intravitreal clindamycin as an adjuvant therapy. CASE REPORT: A 10-day-old infant presented with active retinochoroiditis lesions in both eyes along with hepatosplenomegaly, abdominal distension, and thrombocytopenia. The mother had a history of fever in the third trimester for which she received symptomatic treatment. The infant was treated with systemic anti-toxoplasma therapy along with intravitreal clindamycin in the severely affected eye. There was a significant faster resolution in the retinochoroiditis lesions, which eventually lead to better anatomical and visual outcomes. CONCLUSION AND IMPORTANCE: Active screening and timely intervention of the neonates who are born to mothers with fever during pregnancy can go a long way in preventing unlikely outcomes due to congenital toxoplasma retinochoroiditis. Intravitreal clindamycin can be considered as an adjuvant therapy in selected cases.

Combined rhegmatogenous and tractional retinal detachment in a child with incontinentia pigmenti managed by scleral imbrication with scleral buckle.

We report for the first time a child with incontinentia pigmenti presenting with acute-onset rhegmatogenous retinal detachment in association with pre-existing tractional retinal detachment. Due to the combined nature of this detachment, complex vector forces acting on the retina makes this a difficult to treat situation. A single surgery of modified scleral imbrication with scleral buckle was effective in reattaching the retina by providing a very high buckle indent to accommodate all the complex vector forces. Commonly used procedure of vitrectomy and silicone oil usage was avoided as that often requires multiple surgeries and may result in variable and unpredictable response.

Avascular Peripheral Retina in Infants.

Avascular peripheral retina in an infant is a common characteristic of numerous pediatric retinal vascular disorders and often presents a diagnostic challenge to the clinician. In this review, key features of each disease in the differential diagnosis, from retinopathy of prematurity, familial exudative vitreoretinopathy, Coats disease, incontinentia pigmenti, Norrie disease, and persistent fetal vasculature, to other rare hematologic conditions and telomere disorders, will be discussed by expert ophthalmologists in the field.