Clinical and demographic profile of herpes zoster ophthalmicus: A hospital-based study of 1752 Indian patients.

PURPOSE: To describe the clinical and demographic profile of herpes zoster ophthalmicus (HZO) in patients presenting to a multitier ophthalmology hospital network in India. METHODS: Cross-sectional hospital-based study included 3,004,470 new patients between August 2010 and October 2021. Patients with a clinical diagnosis of HZO in at least one eye were included. Data were collected using an electronic medical record system. RESULTS: In total, 1,752 (0.058%) patients were diagnosed with HZO. Nearly two-thirds were male (63.76%) in the seventh decade of life (339;19.35% patients) with unilateral (98.34%) affliction. Higher prevalence was seen in patients from higher socioeconomic status (0.059%) and metropolitan geography (0.062%). Most common ocular signs included eyelid edema (44.19%), conjunctival congestion (65.69%), punctate keratopathy (23.36%), and anterior uveitis (21.22%). Of the 1,781 eyes, mild/no visual impairment was seen in 952 (53.45%) eyes, moderate in 258 (14.49%) eyes, and severe to blindness in 363 (20.39%) eyes. Oral antivirals were started within 72 h (Group A) in 361 (20.61%) patients and after 72 h in 1391 (79.39%) patients (Group B). Significantly lesser severity of ocular involvement was noted in Group A (P < 0.00001). Surgical intervention was required in 211 (11.85%) eyes. CONCLUSION: HZO more commonly affects males in the seventh decade of life and is predominantly unilateral. It more commonly affects those from higher socioeconomic strata and metropolitan regions. Half of the eyes have mild or no visual impairment, while others have moderate to severe impairment. Institution of antivirals within 72 h is associated with less severe involvement. Surgical intervention is warranted in a tenth of the eyes.

Strategies and Application of Compression Sutures With a Modified Technique for Rapid Resolution of Large (Grade III) Hydrops: A Prospective Interventional Study.

PURPOSE: The aim of this study was to describe the strategies and outcomes, with a modified technique, of compression sutures in large acute hydrops. METHODS: This was a prospective interventional study in 29 eyes of 28 patients who underwent compression sutures using a modified technique. The degree of resolution after surgical intervention was quantified by 3 masked observers, using the slit-lamp photographic documentation and optical coherence tomography. The degree of resolution, best-corrected visual acuity, and complications were analyzed. RESULTS: The mean age was 20.89 (7-46) years. Five patients had pellucid marginal degeneration (pellucid marginal corneal degeneration), 23 had keratoconus, and 1 had posttrauma hydrops. The preoperative visual acuity was hand motions in all eyes. The reduction in edema was 76% on day 1, 91.6% on 6 ± 2 days, 98.6% on 18 ± 3 days from surgical intervention. The baseline pachymetry assessed on optical coherence tomography was beyond measurement in 26 eyes. The mean pachymetry at day 1 was 704 µm (range 480-950) which reduced to 607 (range 422-850) microns at 6 ± 2 days and 518 (range 415-718) microns at 18 ± 3 days postintervention ( P < 0.0001). The mean duration between the surgery and complete suture removal was 48 (35-68) days. No suture-related complications were noted. Twenty eyes could attain good visual rehabilitation with glasses/contact lenses (vision could not be assessed in 5 eyes). Penetrating keratoplasty was performed on 1 patient. CONCLUSIONS: Compression sutures using the modified technique was safe and effective in the rapid resolution of acute hydrops in keratoconus and pellucid marginal corneal degeneration. No complications were noted, and visual restoration with spectacles and contact lenses was satisfactory.

Clinical and Optical Coherence Tomography Correlation of Recurrence Patterns After Femtosecond Laser-Assisted Anterior Lamellar Keratoplasty in Reis-Bucklers Corneal Dystrophy.

PURPOSE: The aim of this study was to report the clinical profile and patterns of recurrence after femtosecond laser-assisted anterior lamellar keratoplasty (FALK) in Reis-Bucklers corneal dystrophy. METHODS: This is a case series of 5 eyes of 4 patients with Reis-Bucklers corneal dystrophy. Clinical images of recurrence were correlated with the high-resolution optical coherence tomography. Histopathologic examination of excised corneal samples was performed when possible. RESULTS: The median time to recurrence was 2 (1-5) years after FALK. Of the 5 eyes, 1 eye had primary FALK, whereas 4 eyes had secondary interventions, which included previous phototherapeutic keratectomy (once in 1 eye and twice in 2 eyes), and previous penetrating keratoplasty, followed by phototherapeutic keratectomy (1 eye). Recurrence was noted at the level of the subepithelium. In addition, 1 eye showed interface deposits along with epithelial downgrowth at the graft-host bed. CONCLUSIONS: The 2 distinct patterns of recurrence noted were at the subepithelial region and the interface. The clinical patterns of recurrence favor an epithelial origin of recurrent deposits.

Band-shaped keratopathy in HNF4A-related Fanconi syndrome: a case report and review of the literature.

BACKGROUND: Fanconi's syndrome (FS) is characterized by type-2 renal tubular acidosis, short stature, and renal rickets, along with glycosuria, aminoaciduria, hypophosphaturia, and urinary bicarbonate wasting. The genetic form of FS has been linked to HNF4A variants. Although additional clinical features such as hearing impairment have recently been associated with HNF4A-linked FS, its ocular manifestation has not been described. MATERIAL AND METHODS: Presenting a case of a 5-year-old male child with bilateral progressive corneal opacification and the presence of bilateral greyish-white deposits in the interpalpebral region since infancy. A next-generation sequencing (NGS)-based genetic testing was performed for the child followed by parental genetic testing for the identified variant. Furthermore, relevant works of literature were reviewed related to this condition. RESULTS: Detailed corneal findings showed a bilateral band-shaped keratopathy (BSK) in the patient. Physical and systemic findings showed signs consistent with FS. Sequencing analysis revealed a novel heterozygous c.635C>T, (p.Pro212Leu) variant in the HNF4A gene in the proband and mother, while the father had a normal genotype. CONCLUSIONS: Our case highlights the occurrence of BSK in an exceptionally rare manifestation of hereditary FS linked to HNF4A gene variant. The variant exists both in proband and asymptomatic mother. Therefore, the variable penetrance which is known to exist in HNF4A is acknowledged in this context. This report suggests the first documented instance establishing a plausible connection between BSK and HNF4A-associated FS, characterized by the variable penetrance attributed to the HNF4A gene.

Characteristics of Corneal Endothelium in Axenfeld Rieger Spectrum.

PURPOSE: The purpose of this study was to compare the corneal endothelial characteristics in Axenfeld anomaly (AXA), Rieger anomaly (RGA), and Axenfeld-Rieger anomaly/syndrome with age-matched healthy controls. METHODS: This is a retrospective, comparative case-control study of 52 eyes of 30 patients with AXA/RGA and AXA/S and 36 controls. RESULTS: Median age at endothelial imaging was 21.5 years (interquartile range, 13.8-33.3 years). In the study group, the mean endothelial cell density (ECD) was 2112.4 ± 78.5 cells/mm 2 , the mean cell area (MCA) was 526.9 ± 28.5 µm 2 , and the coefficient of variation of cell size was 41.2 ± 1.8%. The ECD was significantly (all, P < 0.0001) lower than controls, while MCA ( P < 0.0001), SD of cell size ( P < 0.0001), and maximum cell area ( P = 0.0007) were significantly higher than controls. Four eyes of 3 patients had guttae on slitlamp evaluation and endothelial imaging. There were no differences in the corneal endothelial characteristics among the clinical subtypes. CONCLUSIONS: Patients with AXA, RGA, and Axenfeld-Rieger anomaly/syndrome have lower ECD and increased MCA compared with normal eyes. The reduced ECD associated with inherent anterior segment alterations can predispose to the risk of postcataract surgery endothelial decompensation in these eyes. The association of guttae in some eyes needs further investigational studies.

Novel Proposed Algorithm in Congenital Hereditary Endothelial Dystrophy.

PURPOSE: Congenital hereditary endothelial dystrophy (CHED) is a rare, autosomal recessive, monogenic corneal condition with variable expressivity. Often presents in bilateral symmetrical progressive corneal cloudiness that starts in the early infancy. It is characterized by increased corneal thickness, profound corneal edema, and thickening of the Descemet membrane due to endothelial dysfunction. The published literature lacks uniform guidelines for grading corneal cloudiness and management algorithm for CHED cases. This article focuses on applying newer investigational modalities to fine-tune surgical outcomes and more recent CHED management strategies. METHODS: This comprehensive literature review was performed based on a search on the PubMed database of relevant CHED articles focusing on those published in the last 7 years. A total of around 70 articles were reviewed, and 17 of them were included in this review. These include systemic reviews, randomized controlled clinical trials, cohort studies, case-controlled studies, and case series. RESULTS: Corneal cloudiness grading in CHED using subjective and objective methods using Anterior Segment Optical Coherence Tomography (AS-OCT) and densitometry using Scheimpflug imaging can help select appropriate management plan for CHED cases. DSAEK outscores penetrating keratoplasty with much fewer complications and expedites visual recovery, which helps mitigate amblyopia. CONCLUSION: Managing cases of CHED has been a challenge due to the dilemma in timing and appropriate surgical method selection and lack of definitive medical or other conservative approaches. Currently, DSAEK has shown favorable results in cases of CHED. However, appropriate staging of CHED and selecting the appropriate management approach appears to play a critical role in managing such cases. Besides these, novel treatment modalities such as nonsteroidal anti-inflammatory agents (NSAIDS) that target restoring water-flux activity in subtype of CHED and gene editing using CRISPR-Cas9 are promising paradigm treatment modalities.

Axenfeld-Rieger syndrome in the pediatric population: A review.

Axenfeld-Rieger syndrome (ARS) is a rare autosomal-dominant neurocristopathy that presents with a variety of classical ocular and systemic findings. The pathophysiology of the disease involves anterior segment dysgenesis, and patients may present with ophthalmic complications early in life, including secondary glaucoma, high refractive errors, amblyopia, and permanent visual damage. There are a limited number of studies in the literature that focus primarily on pediatric patients with ARS. The purpose of this article was to review the current literature on clinical presentation, genetic associations, diagnosis, secondary complications, and treatment of ARS in pediatric patients. Evaluating the essential clinical aspects of the disease in children may allow for earlier diagnosis and treatment and prevent visual morbidity from amblyopia and secondary glaucoma that may result in permanent visual damage.

Updates on congenital hereditary endothelial dystrophy.

Congenital hereditary endothelial dystrophy (CHED) is a rare genetic corneal disorder causing progressive cornea clouding and significant visual impairment. CHED remains a leading indication for pediatric corneal transplantation despite its infrequency, particularly in regions with high consanguinity rates like Southeast Asia. Identifying the Solute Carrier Family 4 Member 11 (SLC4A11) gene as the genetic basis of CHED has led to the discovery of it's various genetic variations. However, a comprehensive understanding of its clinical-genetic correlation, pathophysiology, and optimal management is ongoing. This review aims to consolidate current knowledge about CHED, covering its genetic origins, pathophysiological mechanisms, clinical presentation, and management strategies. Surgical intervention, such as penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), and Descemet membrane endothelial keratoplasty (DMEK), remains the primary treatment. DSAEK and DMEK offer advantages over PK, including quicker visual recovery, reduced complications, and longer graft survival, especially in the pediatric age group. The timing of surgical interventions depends on disease severity, age at presentation, comorbidities, and visual potential. Elevated oxidative stress in CHED corneal tissue suggests potential benefits from anti-inflammatory drugs to rescue mutated endothelial cells. Considering the limitations of corneal graft surgeries, exploring novel gene-based molecular therapies are essential for future management. Early diagnosis, appropriate surgical interventions, amblyopia control, and genetic counseling for predictive analysis are pivotal for optimizing CHED management. A multidisciplinary approach involving ophthalmologists, researchers, and genetic counselors is essential for precise diagnosis and optimal care for CHED patients.

Objectively measuring anterior segment alterations in the eyes of mucopolysaccharidoses: Its utility in early diagnosis of glaucoma.

Purpose: Our study aimed to evaluate the utility of the anterior segment morphometry for objectively assessing anterior segment architectural changes of corneal clouding in the mucopolysaccharidoses (MPS) cohort and to investigate whether these measurements correlate with the slit-lamp findings on the cornea and early diagnosis of glaucoma. Methods: This retrospective study involved 70 eyes of 35 children with cloudy cornea due to MPS variants. Anterior segment architectural alterations were measured using anterior segment imaging and biometry in MPS children and compared with controls. Results: Mean age of the cohort at the time of assessment was 7.9 ± 4.5 years. Males constituted two-thirds of the cohort. Variants of MPS with cloudy cornea were as follows: Type I (62%), Type IV (11%), and Type VI (22%). Morphometric measurements were available in 22 eyes of 11 MPS children and an age-matched healthy control group. There were significant differences between MPS cohort and controls in refraction in Diopters (5.03 ± 0.39 and 0.01 ± 0.04; P < 0.0001), axial length (AXL) in mm (21.39 ± 0.28 and 23.04 ± 0.28; P = 0.0002), average keratometry in Diopters (40.67 ± 0.44 and 42.83 ± 0.44; P < 0.0001), anterior chamber depth (ACD) in mm (2.92 ± 0.07 and 3.65 ± 0.07; P < 0.0001), and intraocular pressure (IOP) in mmHg (25.2 ± 2.0 and 14.1 ± 2.3; P = 0.0003). Secondary glaucoma was observed in 28% of the MPS cohort. Conclusion: The anterior segment morphometry in the cloudy cornea due to MPS provides an objective measurement of anterior segment architectural changes, thus diagnosing early-onset secondary glaucoma. These findings highlight that cloudy cornea due to MPS variants merits close monitoring throughout life.

Selective Endothelialectomy in Peters Anomaly: A Novel Surgical Technique and Its Clinical Outcomes in Children.

PURPOSE: This study describes the surgical outcomes of selective endothelialectomy in Peters anomaly (SEPA), a relatively new technique to manage Peters anomaly (PA). METHODS: This study included 34 eyes of 28 children who had a visually significant posterior corneal defect due to PA and underwent SEPA between 2012 and 2019. A selective endothelialectomy from the posterior corneal defect was performed while preserving Descemet membrane. The primary outcome measure was the resolution of corneal opacification. The secondary outcome measures were functional vision, complications, and risk factors for failure. RESULTS: At a mean postoperative follow-up of 0.96 ± 0.20 years, 29 eyes (85.3%) maintained a successful outcome. Mean preoperative and postoperative best-corrected visual acuities were 2.55 ± 0.13 and 1.78 ± 0.13 ( P < 0.0001), respectively. Ambulatory functional visual improvement was seen in 97%, and 23% attained vision ranging between 20/190 and 20/50. Corneal opacification failed to clear in 5 eyes (15%). Risk factors associated with surgical failure were female sex ( P = 0.006), disease severity ( P < 0.0001), glaucoma ( P = 0.001), and additional interventions after SEPA ( P = 0.002). In multivariate analysis, only disease severity (ie, a type 2 PA) was a significant risk factor for the failure of SEPA. There were no sight-threatening complications. CONCLUSIONS: SEPA is a safe and effective technique in select cases of posterior corneal defect due to PA. SEPA could be a potential surgical alternative to pediatric keratoplasty or optical iridectomy in children with central corneal opacification smaller than 7 mm due to PA.

Identification and in silico analysis of a spectrum of SLC4A11 variations in Indian familial and sporadic cases of congenital hereditary endothelial dystrophy.

BACKGROUND: Congenital hereditary endothelial dystrophy (CHED) is a rare form of corneal dystrophy caused by SLC4A11 gene variations. This study aims to find the genetic alterations in SLC4A11, in two Indian familial CHED cases with affected members n = 3 and n = 2 respectively and five sporadic CHED cases using direct sequencing, followed by in silico analysis and characterization of the identified variants. RESULTS: All three affected members of the first CHED family were identified with a novel homozygous c.1514C > G (p.Ser489Trp) variation while second family showed presence of a compound heterozygous variation c.529A > C (p.Arg161Arg) + c.2461insT (p.Val805fs). Among five sporadic cases, two showed novel changes, homozygous c.1487G > T (p.Ser480Ile) and c.620-2A > G, while the other one had previously reported homozygous c.2653C > T (p.Arg869Cys) variation. The remaining two cases did not reveal the presence of SLC4A11-related pathogenic variations. The identified variations were excluded from the Indian control (n = 80). In silico analysis using homology-based protein modeling and pathogenicity prediction tools, which revealed these alterations as pathogenic, changing their protein stability, local flexibility, residue contact clashes, and the hydrogen bond interactions. CONCLUSIONS: This study contributed to the CHED mutational spectrum, adding four novel variations and confirming a previously reported one. It demonstrates different type of variations in CHED cases, including coding, non-coding, homozygous, synonymous, and compound heterozygous variations. The identified variations revealed different degrees of pathogenic effects in silico. Moreover, two sporadic cases could not be identified with pathogenic variation emphasizing the involvement of other genes or genetic mechanisms.

New Frontier in the Management of Corneal Dystrophies: Basics, Development, and Challenges in Corneal Gene Therapy and Gene Editing.

ABSTRACT: Corneal dystrophies represent a group of heterogeneous hereditary disorders causing progressive corneal opacification and blindness. Current corneal transplant management for corneal dystrophies faces the challenges of repeated treatments, complex surgical procedures, shortage of appropriate donor cornea, and, more importantly, graft rejection. Genetic medicine could be an alternative treatment regime to overcome such challenges. Cornea carries promising scope for a gene-based therapy involving gene supplementation, gene silencing, and gene editing in both ex vivo and in vivo platforms. In the cornea, ex vivo gene therapeutic strategies were attempted for corneal graft survival, and in vivo gene augmentation therapies aimed to prevent herpes stromal keratitis, neovascularization, corneal clouding, and wound healing. However, none of these studies followed a clinical trial-based successful outcome. CRISPR/Cas system offers a broad scope of gene editing and engineering to correct underlying genetic causes in corneal dystrophies. Corneal tissue--specific gene correction in vitro with minimal off-target effects and optimal gene correction efficiency followed by their successful surgical implantation, or in vivo CRISPR administration targeting pathogenic genes finds a way to explore therapeutic intervention for corneal dystrophies. However, there are many limitations associated with such CRISPR-based corneal treatment management. This review will look into the development of corneal gene therapy and CRISPR-based study in corneal dystrophies, associated challenges, potential approaches, and future directions.

Update on the genetics of corneal endothelial dystrophies.

Corneal endothelial dystrophies are a heterogeneous group of diseases with different modes of inheritance and genetic basis for each dystrophy. The genes associated with these diseases encode transcription factors, structural components of the stroma and Descemet membrane, cell transport proteins, and others. Congenital hereditary endothelial dystrophy (CHED) is associated with mutations in two genes, OVOL2 and SLC4A11, for dominant and recessive forms of CHED, respectively. Mutations in three genes are known to cause posterior polymorphous corneal dystrophy (PPCD). They are OVOL2 (PPCD1), ZEB1 (PPCD3), and GRHL1 (PPCD4). The PPCD2 locus involving the collagen gene COL8A2 on chromosome 1 is disputed due to insufficient evidence. Mutations in the COL8A2 gene are associated with early-onset Fuchs' endothelial corneal dystrophy (FECD). Several genes have been associated with the more common, late-onset FECD. Alterations in each of these genes occur in a fraction of patients, and the most prevalent genetic alteration in FECD patients across the world is a triplet repeat expansion in the TCF4 gene. Knowledge of the genetics of corneal endothelial dystrophies has considerably advanced within the last decade and has contributed to better diagnosis of these dystrophies as well as opened up the possibility of novel therapeutic approaches based on the molecular mechanisms involved. The functions of genes identified to date provide insights into the pathogenic mechanisms involved in each disorder.

Clinical and visual electrophysiological characteristics of vitelliform macular dystrophies in the first decade of life.

Purpose: To evaluate patterns of pediatric vitelliform macular dystrophy (PVMD). Methods: This is a retrospective analysis of Indian children with vitelliform macular dystrophy (VMD) presenting within the first decade of life. Records were evaluated for clinical findings, family screening, and investigative findings including optical coherence tomography (OCT), fundus autofluorescence (FAF), full-field electroretinogram (ERG) and electrooculogram (EOG). Electrophysiology was scrutinized and audited for acquisition and interpretation errors. Findings on follow-up were also recorded. Results: 46 eyes of 24 patients were included. Mean age at presentation was 7.17 ± 2.17 years. Mean follow-up duration was 1.55 ± 1.69 years. Best disease was the commonest type of VMD detected (21 patients), while autosomal recessive bestrophinopathy was seen in three cases. Mean logMAR BCVA was 0.364 which decreased to 0.402 on follow-up. Hyperopia was noted in 29 out of 46 eyes (mean being +3.87 D, range ebing +0.75 to +8.75 D). Four eyes of four children had choroidal neovascular membrane at presentation, while another child developed while in follow-up. Solid type subretinal deposit was the commonest OCT finding (n = 29/38) and central hyper FAF was the commonest pattern (n = 18/32). EOG was available for review in 32 eyes, but was unreliable in 11 eyes. Seven eyes demonstrated complete absence of light rise on EOG. Conclusion: PVMD can present in advanced forms. Progression to complications with loss of visual acuity can happen within the first decade of life. EOG shows grossly suppressed waveforms in the light phase in a large number of such children.

Neurotization of the human cornea - A comprehensive review and an interim report.

We present a comprehensive review of existing literature on surgical corneal neurotization (SCN) as a treatment modality for neurotrophic keratopathy (NK) with an interim report of seven cases where SCN was performed using the indirect approach and followed up till 18 months postoperatively to look for improvement in ocular surface, corneal sensations, and nerve regeneration by using in vivo confocal microscopy (IVCM). A literature search was performed for publications with keywords "corneal nerves," "neurotization," "esthesiometry," "corneal anesthesia," and "neurotrophic keratopathy." All literature available till December 31, 2020 was reviewed and included to describe NK and its management options, particularly SCN. NK is associated with absent or reduced corneal sensations and is managed using a step-ladder algorithm ranging from medical management for symptomatic relief to surgical corneal neurotization. Both direct and indirect approaches of SCN have a favorable outcome with reduced surgical morbidity in the indirect approach using sural nerve graft. Post neurotization, corneal sensation recovery may take up to 3-6 months, while nerve regeneration on confocal microscopy can take as long as 6 months-1 year.

Role of AS-OCT in Managing Corneal Disorders.

Optical coherence tomography (OCT) is analogous to ultrasound biometry in the cross sectional imaging of ocular tissues. Development of current devices with deeper penetration and higher resolution has made it popular tool in clinics for visualization of anterior segment structures. In this review, the authors discussed the application of AS-OCT for diagnosis and management of various corneal and ocular surface disorders. Further, recent developments in the application of the device for pediatric corneal disorders and extending the application of OCT angiography for anterior segment are introduced.