Recurrent retinal detachment in Stickler Syndrome.

OBJECTIVE: To assess clinical factors leading to recurrent retinal detachment (RD) and characteristics of recurrence in patients with Stickler Syndrome. METHODS: Retrospective case series study of patients with clinical diagnosis of Stickler Syndrome who underwent rhegmatogenous RD repair. Recurrent RD after initial surgery was categorized as "early" if the recurrence was within 1 year or "late" if greater than 1 year. RESULTS: Thirty eyes from 22 patients underwent rhegmatogenous RD repair. For initial repair, 13 eyes underwent pars plana vitrectomy combined with scleral buckling (PPV/SB), 16 eyes underwent primary scleral buckling (SB), and 1 eye underwent pneumatic retinopexy (PnR). Recurrent RD occurred in 6 (46%) PPV/SB eyes (5 early and 1 late), 10 (63%) SB eyes (3 early and 7 late), and 0 (0%) PnR eyes (p = 0.61). PPV/SB was preferred for eyes presenting with total detachment (82%), giant retinal tears (100%), and proliferative vitreoretinopathy (PVR) (80%). For eyes with early recurrent RD, 6 (75%) had PVR leading to recurrence. For eyes with late recurrent RD, 7 (87.5%) developed a new retinal break leading to recurrence, including 4 with a break posterior to the buckle indentation apex. At last follow-up, median LogMAR visual acuity was 0.68 for eyes with recurrent RD compared to 0.29 for eyes without recurrence (p = 0.27). CONCLUSIONS: Early recurrent RD was mostly caused by PVR, while late recurrent RD was mostly due to new retinal breaks. Eyes with seemingly uncomplicated rhegmatogenous RD repair with primary SB remained at high risk for late re-detachment.

Harnessing Generalizable Real-World Ophthalmic Big Data: Descriptive Analysis of the Bodhya Eye Consortium Model for Collaborative Research.

BACKGROUND: Eye care organizations and professionals worldwide are increasingly focusing on bridging the gap between population health and medical practice. Recent advances in genomics and anthropology have revealed that most Indian groups trace their ancestry to a blend of 2 genetically distinct populations: Ancestral North Indians, who share genetic affinities with Central Asians, Middle Easterners, Caucasians, and Europeans; and Ancestral South Indians, genetically distinct from groups outside the Indian subcontinent. Studies conducted among North Indian populations can therefore offer insights that are potentially applicable to these diverse global populations, underscoring significant implications for global health. OBJECTIVE: The Bodhya Eye Consortium is a collaboration among 8 high-volume nonprofit eyecare organizations from across North India. The consortium aims to harness real-world data consistently and with assured quality for collaborative research. This paper outlines the formation of the consortium as a proposed model for controlled collaborative research among the leading eyecare organizations of North India. METHODS: We detail the creation and effective implementation of a consortium following a structured road map that included planning and assessment, establishing an exploratory task force, defining specialty areas, setting objectives and priorities, and conducting a SWOT (strengths, weaknesses, opportunities, and threats) analysis. Central to this process was a comprehensive data audit aimed at standardizing data collection across all participating organizations. RESULTS: The consortium currently comprises 9 organizations, each represented in the governance structure by the Governing Council. Scientific standards for published research are established and overseen by the Scientific Committee, while the Conflict Resolution Committee manages any unresolved disputes. The consortium's working groups, organized by various eyecare specialties, collaborate on research projects through virtual interactions. A foundational step in this process was the organizationwide data audit, which revealed that most organizations complied with accurate and standardized data collection practices. Organizations with deficiencies in data completeness developed action plans to address them. Subsequently, the consortium adopted data collection proformas, contributing to the publication of high-quality manuscripts characterized by low dropout rates. CONCLUSIONS: The collaborative research conducted by the Bodhya Eye Consortium-a group of high-volume eyecare organizations primarily from North India-offers a unique opportunity to contribute to scientific knowledge across various domains of eyecare. By leveraging the established heterogeneity of anthropological and genomic origins within the population, the findings can be generalizable, to some extent, to European, Middle Eastern, and European American populations. This access to potentially invaluable, generalizable data has significant global health implications and opens possibilities for broader collaboration. The model outlined in this descriptive paper can serve as a blueprint for other health care organizations looking to develop similar collaborations for research and knowledge sharing.

Corneal Collagen Cross-linking for Keratoconus in Pediatric and Developmentally Delayed Patients.

PURPOSE: Corneal cross-linking (CXL) is the standard of care in patients with keratoconus but presents unique challenges in children and developmentally delayed patients. We present our clinical decision-making algorithm, CXL surgical technique, and outcomes in these groups. METHODS: A retrospective chart review was undertaken at a tertiary referral center of all patients who underwent CXL for keratoconus at University of Pittsburgh Medical Center (UPMC) Children's Hospital of Pittsburgh between October 1, 2017, and April 1, 2021. Demographic information along with preoperative, intraoperative, and postoperative ophthalmic examination findings were collected. The main outcome measures were indications of CXL, postoperative complications, and visual acuity (VA). RESULTS: Forty-eight eyes of 34 patients [21 patients (30 eyes) with developmental delay (DD) and 13 patients (18 eyes) with no DD (NDD)] underwent epithelium-off, standard CXL. General anesthesia was used for CXL in all patients except for 3 with NDD. A temporary central tarsorrhaphy was performed in all patients with DD and 7 patients with NDD. The remaining got a bandage contact lens. There were no immediate postoperative complications. A trend toward improvement in VA was noted postoperatively. The mean logMAR VA (with habitual correction) was 0.67 preoperatively and 0.57 postoperatively (P = 0.3) in DD and 0.52 and 0.36, respectively (P = 0.13), in NDD. CONCLUSIONS: This retrospective review presents a technique for assessment and treatment of keratoconus in children and those with DD. Our technique ensures timely diagnosis and provides a safe method for CXL in these groups. Temporary central tarsorrhaphy is a well-tolerated option to reduce postoperative pain.

Early diagnosis and treatment by newborn screening (NBS) or family history is associated with improved visual outcomes for long-chain 3-hydroxyacylCoA dehydrogenase deficiency (LCHADD) chorioretinopathy.

Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) is the only fatty acid oxidation disorder to develop a progressive chorioretinopathy resulting in vision loss; newborn screening (NBS) for this disorder began in the United States around 2004. We compared visual outcomes among 40 participants with LCHADD or trifunctional protein deficiency diagnosed symptomatically to those who were diagnosed via NBS or a family history. Participants completed ophthalmologic testing including measures of visual acuity, electroretinograms (ERG), fundal imaging, contrast sensitivity, and visual fields. Records were reviewed to document medical and treatment history. Twelve participants presented symptomatically with hypoglycemia, failure to thrive, liver dysfunction, cardiac arrest, or rhabdomyolysis. Twenty eight were diagnosed by NBS or due to a family history of LCHADD. Participants diagnosed symptomatically were older but had similar percent males and genotypes as those diagnosed by NBS. Treatment consisted of fasting avoidance, dietary long-chain fat restriction, MCT, C7, and/or carnitine supplementation. Visual acuity, rod- and cone-driven amplitudes on ERG, contrast sensitivity scores, and visual fields were all significantly worse among participants diagnosed symptomatically compared to NBS. In mixed-effects models, both age and presentation (symptomatic vs. NBS) were significant independent factors associated with visual outcomes. This suggests that visual outcomes were improved by NBS, but there was still lower visual function with advancing age in both groups. Early diagnosis and treatment by NBS is associated with improved visual outcomes and retinal function compared to participants who presented symptomatically. Despite the impact of early intervention, chorioretinopathy was greater with advancing age, highlighting the need for novel treatments.

Calcified Sclero-Choroidal Choristomas in Mosaic RASopathies: A Description of a New Imaging Sign.

PURPOSE: To evaluate the imaging and clinical features of unusual calcified lesions seen in the fundus of patients with mosaic RASopathy. DESIGN: Single-center retrospective observational study. SUBJECTS: Ten eyes with calcified fundus lesions in 7 patients with mosaic RASopathy. METHODS: The lesions were evaluated with fundus photography, oral fundus fluorescein angiography, B-scan ultrasonography, magnetic resonance imaging (MRI), and computed tomography (CT) scan where available. MAIN OUTCOME MEASURES: The imaging characteristics of calcified fundus lesions were assessed. RESULTS: We found 7 patients with mosaic RASopathies, 5 men and 2 women (3 with linear sebaceous nevus syndrome, 3 with oculoectodermal syndrome, and 1 with encephalocraniocutaneous lipomatosis) with molecular confirmation in 5 cases, all 5 having KRAS-pathogenic variants. Calcified fundus lesions were identified in 10 eyes (bilateral in 3 patients), appearing as slightly elevated, creamy-yellow lesions around or adjacent to the optic nerve, extending supero-nasally; all but 2 of these lesions involved both the choroid and sclera, with 2 of them only involving the sclera at the time of examination. One case developed a choroidal neovascular membrane necessitating intravitreal bevacizumab injections. All 7 patients had B-scan ultrasonography, and the lesion appeared as a hyperechogenic area with an acoustic shadow posteriorly despite reduced gain. Five patients had MRI, and where fundus lesions were present, there was a focal defect in the sclero-choroidal layer. Four patients had a CT scan, and all 4 showed calcifications affecting both the posteromedial sclero-choroid and adjacent medial rectus muscle. Two of these patients had normal eye movements, 1 had a unilateral fixed adducted eye and a vestigial fibrous medial rectus muscle seen in imaging and intraoperatively, and the fourth had marked exotropia with a right gaze deficit affecting both eyes. CONCLUSIONS: We propose that the lesions seen in this cohort are calcified sclero-choroidal choristomas and should be suspected in mosaic RASopathies when creamy-yellow lesions are seen in the fundus. If identified, the possibility of choroidal neovascularization should be considered during follow-up. In all cases where a CT scan was performed, a novel sign of sclero-muscular calcification involving the medial rectus muscle was seen. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

IC3D Classification of Corneal Dystrophies-Edition 3.

PURPOSE: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature. METHODS: Peer-reviewed publications from 2014 to 2023 were evaluated. The new information was used to update the anatomic classification and each of the 22 standardized templates including the level of evidence for being a corneal dystrophy [from category 1 (most evidence) to category 4 (least evidence)]. RESULTS: Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( COL17A1 mutations, chromosome 10). Signs and symptoms are similar to Franceschetti corneal dystrophy, dystrophia Smolandiensis, and dystrophia Helsinglandica, category 4. Lisch epithelial corneal dystrophy, previously reported as X-linked, has been discovered to be autosomal dominant ( MCOLN1 mutations, chromosome 19). Classic lattice corneal dystrophy (LCD) results from TGFBI R124C mutation. The LCD variant group has over 80 dystrophies with non-R124C TGFBI mutations, amyloid deposition, and often similar phenotypes to classic LCD. We propose a new nomenclature for specific LCD pathogenic variants by appending the mutation using 1-letter amino acid abbreviations to LCD. Pre-Descemet corneal dystrophies include category 1, autosomal dominant, punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD) ( PRDX3 mutations, chromosome 10). Typically asymptomatic, it can be distinguished phenotypically from pre-Descemet corneal dystrophy, category 4. We include a corneal dystrophy management table. CONCLUSIONS: The IC3D third edition provides a current summary of corneal dystrophy information. The article is available online at https://corneasociety.org/publications/ic3d .

A proposal for an updated staging system for LCHADD retinopathy.

OBJECTIVE: To develop an updated staging system for long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency (LCHADD) chorioretinopathy based on contemporary multimodal imaging and electrophysiology. METHODS: We evaluated forty cases of patients with genetically confirmed LCHADD or trifunctional protein deficiency (TFPD) enrolled in a prospective natural history study. Wide-field fundus photographs, fundus autofluorescence (FAF), optical coherence tomography (OCT), and full-field electroretinogram (ffERG) were reviewed and graded for severity. RESULTS: Two independent experts first graded fundus photos and electrophysiology to classify the stage of chorioretinopathy based upon an existing published system. With newer imaging modalities and improved electrophysiology, many patients did not fit cleanly into a single traditional staging group. Therefore, we developed a novel staging system that better delineated the progression of LCHADD retinopathy. We maintained the four previous delineated stages but created substages A and B in stages 2 to 3 to achieve better differentiation. DISCUSSION: Previous staging systems of LCHADD chorioretinopathy relied on only on the assessment of standard 30 to 45-degree fundus photographs, visual acuity, fluorescein angiography (FA), and ffERG. Advances in recordings of ffERG and multimodal imaging with wider fields of view, allow better assessment of retinal changes. Following these advanced assessments, seven patients did not fit neatly into the original classification system and were therefore recategorized under the new proposed system. CONCLUSION: The new proposed staging system improves the classification of LCHADD chorioretinopathy, with the potential to lead to a deeper understanding of the disease's progression and serve as a more reliable reference point for future therapeutic research.

Variable Phenotype of Congenital Corneal Opacities in Biallelic CYP1B1 Pathogenic Variants.

PURPOSE: The aim of this study is to describe the variable phenotype of congenital corneal opacities occurring in patients with biallelic CYP1B1 pathogenic variants. METHODS: A retrospective chart review was conducted to identify patients with congenital corneal opacities and CYP1B1 pathogenic variants seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, anterior segment optical coherence tomography, histopathologic images, and details of genetic testing were reviewed. RESULTS: Three children were identified. All presented with raised intraocular pressure. Two patients showed bilateral limbus-to-limbus avascular corneal opacification that did not resolve with intraocular pressure control; 1 showed unilateral avascular corneal opacity with a crescent of clear cornea, iridocorneal adhesions, iridolenticular adhesions, and classical features of congenital glaucoma in the fellow eye (enlarged corneal diameter, Haab striae, and clearing of the corneal clouding with appropriate intraocular pressure control). The first 2 patients were visually rehabilitated with penetrating keratoplasty. Histopathology revealed distinct features: a variably keratinized epithelium; a thick but discontinuous Bowman-like layer with areas of disruption and abnormal cellularity; Descemet membrane, when observed, showed reduced endothelial cells; and no pathological changes of Haab striae were identified. Two patients had compound heterozygous pathogenic variants in CYP1B1 causing premature stop codons, whereas 1 was homozygous for a pathogenic missense variant. CONCLUSIONS: Congenital corneal opacities seen in biallelic CYP1B1 pathogenic variants have a variable phenotype. One is that commonly termed as Peters anomaly type 1 (with iridocorneal adhesions, with or without iridolenticular adhesions) and the other is a limbus-to-limbus opacity, termed CYP1B1 cytopathy. Clinicians should be aware of this phenotypic variability.

Pediatric oral fluorescein angiography: a retrospective review from a single institution.

PURPOSE: To describe our experience with locally developed evidence-based guidelines for oral fluorescein angiography (FA) for retinal imaging in children. METHODS: The medical records of consecutive pediatric patients (≤18 years of age) at University of Pittsburgh Medical Center Children's Hospital Eye Center who underwent oral FA between November 1, 2018, and April 1, 2022, were reviewed retrospectively. Adherence to or deviation from the guidelines was noted at the time of testing. RESULTS: A total of 55 patients aged 3-18 with 79 examinations were included. No patient was excluded from the retrospective case review because of lack of recorded data. The main indications for oral FA included uveitis, retinal vasculopathy, disk pathology, and retinal lesions. Three children had transient side effects, and 1 had delayed urticaria 4 hours after examination. No child had anaphylaxis. One patient had suboptimal imaging due to nonadherence to the guidelines-recommended fasting protocol. All other examinations (78/79), where guidelines were followed, provided images adequate for clinical decision making. CONCLUSIONS: Based on our experience, we recommend that oral FA be considered, especially in children where intravenous access is less well tolerated while awake. Informed consent that includes the possibility of delayed side effects is advisable.

IMI-Management and Investigation of High Myopia in Infants and Young Children.

Purpose: The purpose of this study was to evaluate the epidemiology, etiology, clinical assessment, investigation, management, and visual consequences of high myopia (≤-6 diopters [D]) in infants and young children. Findings: High myopia is rare in pre-school children with a prevalence less than 1%. The etiology of myopia in such children is different than in older children, with a high rate of secondary myopia associated with prematurity or genetic causes. The priority following the diagnosis of high myopia in childhood is to determine whether there is an associated medical diagnosis that may be of greater overall importance to the health of the child through a clinical evaluation that targets the commonest features associated with syndromic forms of myopia. Biometric evaluation (including axial length and corneal curvature) is important to distinguishing axial myopia from refractive myopia associated with abnormal development of the anterior segment. Additional investigation includes ocular imaging, electrophysiological tests, genetic testing, and involvement of pediatricians and clinical geneticists is often warranted. Following investigation, optical correction is essential, but this may be more challenging and complex than in older children. Application of myopia control interventions in this group of children requires a case-by-case approach due to the lack of evidence of efficacy and clinical heterogeneity of high myopia in young children. Conclusions: High myopia in infants and young children is a rare condition with a different pattern of etiology to that seen in older children. The clinical management of such children, in terms of investigation, optical correction, and use of myopia control treatments, is a complex and often multidisciplinary process.

Thygeson's superficial punctate keratitis in children.

OBJECTIVE: To describe the first paediatric case series of Thygesons' superficial punctate keratitis (TSPK) with management outcomes. METHODS: A retrospective chart review was done for all children either diagnosed at initial presentation or referred with TSPK from 01/2012 to 08/2021 at a tertiary children's hospital. Records were assessed for signs, symptoms, diagnosis, steroid and cyclosporine 0.05% use. The main outcome measures were visual acuity, treatment response and total steroid exposure. RESULTS: Fifteen children (7 females), mean age at presentation 8 ± 4 years were included. All had bilateral disease and a BCVA of >20/40 in the better eye. All patients received topical fluorometholone 0.1%, (FML) initially. 80% had a good response to FML. Corneal scraping was done to exclude infectious causes in four cases due to poor initial response or clinical suspicion. All 4 needed EUA for scraping and anterior segment OCT, after which 2 had molecularly confirmed TGFBI-related stromal dystrophy. For the rest, slow steroid taper was done every 4-6 weeks and recurrences were treated by increasing steroid frequency. Cyclosporine 0.05% was started in nine patients (69%), 8 ± 6 months after initial presentation. The decrease in total steroid exposure per week after starting cyclosporine was statistically significant (p < 0.05). CONCLUSION: Children with TSPK respond quickly to steroids, however, recurrences are common, necessitating a slow taper. Non-response to steroid needs careful reconsideration of the diagnosis and may necessitate the use of an EUA. Using cyclosporine 0.05% reduces the total steroid exposure in TSPK.

OCT Angiography in Noninfectious Uveitis: A Description of Five Cases and Clinical Applications.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a noninvasive imaging modality used to analyze the retinochoroidal vasculature and detect vascular flow. The resulting images can be segmented to view each vascular plexus individually. While fluorescein angiography is still the gold standard for the diagnosis of posterior uveitis, it has limitations, and can be replaced by OCTA in some cases. METHODS: This case series describes five patients with posterior noninfectious uveitis and their description by OCTA. RESULTS: Cases included lupus retinopathy (n = 1) for which OCTA showed ischemic maculopathy as areas of flow deficit at the superficial and deep capillary plexus; choroidal granulomas (n = 1) with a non-detectable flow signal in the choroid; active punctate inner choroiditis and multifocal choroiditis (n = 1) with OCTA that showed active inflammatory chorioretinal lesions as non-detectable flow signals in choriocapillaris and choroid; dense type 2 inflammatory secondary neovascularization (n = 1) associated with active choroiditis; and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1) without flow abnormalities at the superficial and deep retinal plexuses but non-detectable flow at the levels of the choriocapillaris and choroid. CONCLUSIONS: Ophthalmologists can use OCTA to identify inflammatory changes in retinal and choroidal vasculature, aiding in the diagnosis, management, and monitoring of posterior uveitis.

Digital eye strain in young screen users: A systematic review.

Digital eye strain (DES) or computer vision syndrome (CVS) is a phenomenon linked to ever increasing digital screen use globally, affecting a large number of individuals. Recognizing causative and alleviating factors of DES may help establish appropriate policies. We aimed to review factors that aggravate or alleviate DES symptoms in young, i.e. pre-presbyopic (< 40 years old), digital device users. We searched PubMed, Scopus, EMBASE, Cochrane, Trip Database, and grey literature up to 1st July 2021. Among a plethora of studies with heterogeneous diagnostic criteria for DES, we only included those using a validated questionnaire for the diagnosis and evaluating associated factors in young subjects. Relevant data were extracted, risk of bias assessment of the included studies and GRADE evaluation of each outcome were performed. Ten studies were included (five interventional, five observational) involving 2365 participants. Evidence coming from studies with moderate risk of bias suggested that blue-blocking filters do not appear to prevent DES (2 studies, 130 participants), while use of screens for > 4-5 h/day (2 studies, 461 participants) and poor ergonomic parameters during screen use (1 study, 200 participants) are associated with higher DES symptoms' score. GRADE evaluation for the outcomes of blue-blocking filters and duration of screen use showed low to moderate quality of evidence. It appears advisable to optimize ergonomic parameters and restrict screen use duration, for minimizing DES symptoms. Health professionals and policy makers may consider recommending such practices for digital screen users at work or leisure. There is no evidence for use of blue-blocking filters.

Corneal Plana-Like Phenotype With Peripheral Scleralization Associated With a Pathogenic Variant of PITX2 : A Case Report.

PURPOSE: The aim of this study was to report a case of corneal plana-like phenotype with bilateral peripheral scleralization associated with a PITX2 pathogenic variant. METHODS: Clinical findings were obtained by ophthalmologic examination. Molecular diagnosis was performed by whole-exome sequencing in the patient and his parents. RESULTS: A 12-month-old male patient present with bilateral peripheral corneal scleralization, corneal plana-like phenotype, and iris hypoplasia. The genetic analysis revealed a de novo PITX2 pathogenic variant (c.323G>A, p.R108H). CONCLUSIONS: PITX2 c.323G>A (p.R108H) can be associated with a unique corneal plana-like phenotype with peripheral scleralization, and thus, PITX2 should be targeted in genetic testing of this specific phenotype.

Technique for the Management of Extensive Ocular Surface Lipodermoid Involving the Cornea of Children.

PURPOSE: Ocular surface lipodermoids with corneal involvement may require surgical intervention; if deep, ocular surface reconstruction with lamellar corneal tissue or amniotic membrane may be needed. We describe a staged technique using autologous ipsilateral simple limbal epithelial transplantation. METHODS: After verifying sparing of Descemet membrane, the conjunctival portion of the lipodermoid was debulked in the first stage. Six weeks later, the corneal portion was excised, followed by autologous ipsilateral simple limbal epithelial transplantation to promote rapid reepithelialization of the residual stromal bed. Temporary tarsorrhaphy was used for patient comfort and to expedite ocular surface healing. RESULTS: Three eyes of 3 children with grade III large ocular surface lipodermoids that encroached the visual axis and hindered proper eyelid closure underwent surgery without complications. In all cases, the visual axis was cleared and eyelid closure was improved. At the last follow-up (mean 35.7 months, median 36.0 months), the bed of the original dermoid showed minimal haze in 1 case, while 2 eyes developed small pseudopterygium; best spectacle-corrected visual acuity improved from 20/200 to 20/70 in the first case, from fix and follow to 20/50 in the second case, and remained fix and follow in the last case, but this child had congenital hydrocephalus with severe developmental delay. CONCLUSIONS: This surgical technique is a promising option for children with grade III large ocular surface lipodermoids given its effectiveness in clearing the visual axis and in improving eyelid closure. Moreover, it does not require lamellar corneal transplantation or intervention to the fellow eye.

The influence of congenital corneal opacity on ERGs obtained using an abbreviated protocol.

BACKGROUND: Visual electrophysiology may be used to assess visual potential in infants with congenital corneal opacities (CCO). It is essential to recognize confounding effects from these opacities on the flash electroretinogram (ERG). METHODS: ERGs were recorded in awake children employing skin electrodes placed at the lower eyelid crease, both referred to a midfrontal electrode (Fz). A hand-held stimulator was used to present a mixed rod-cone and a dim white stimulus. Recordings were carried out before and after penetrating keratoplasty (PK), when performed. RESULTS: Five infants under the age of 12 months with visually significant CCO were evaluated. In all cases, initial ERGs employing the mixed rod-cone stimulus showed well-defined a-wave with reduced amplitude b-wave. Reduction of stimulus intensity resulted in an increase in the b-wave and normalization of the b:a ratio from 1.1 (range 0.7 to 1.3) to 2.8 (range 1.5 to 4.3). In three cases who underwent PK, the postoperative ERGs recorded with a mixed rod-cone stimulus were normal in waveform shape with a mean b:a ratio of 2.0 (range 1.7 to 3.0). CONCLUSION: Selective reduction of the scotopic bright flash ERG b-wave is typically caused by retinal dysfunction that is post-phototransduction or inner retinal. In infants with CCO, scotopic ERGs to bright flashes can show a reduced b:a ratio that improves or normalizes either after PK or stimulus intensity reduction. The study highlights that media opacity can contribute to the generation of an ERG with reduced b-wave in the absence of inner retinal dysfunction.

Congenital Corneal Opacity in 22q11.2 Deletion Syndrome: A Case Series.

PURPOSE: The purpose of this study was to describe the deep phenotype of congenital corneal opacities (CCO) in patients with 22q11.2 deletion syndrome (22q11.2 DS) and to identify putative regions or genes that could explain the CCO. METHODS: A retrospective chart review was conducted to identify patients with 22q11.2 DS seen in the ophthalmology clinic of a tertiary referral children's hospital. Thirty patients were identified, with molecular confirmation. Twenty-six did not show structural anterior segment anomalies aside from posterior embryotoxon (n = 4), whereas 4 had bilateral CCO, of which 3 had preoperative images. We reviewed medical, operative, and pathology reports; anterior segment optical coherence tomography; high-frequency ultrasound; histopathologic slides; and genetic testing. To identify putative genes responsible for CCO, chromosomal breakpoints in patients with and without CCO were compared. RESULTS: In the 3 patients with preoperative imaging and CCO, a pattern of paracentral corneal opacification with central clearing accompanied by iridocorneal or keratolenticular adhesions was observed. Anterior segment optical coherence tomography and histopathologic images showed central stromal thinning with a residual structure consistent with Descemet membrane. One patient presented at birth with unilateral corneal perforation, suggestive of likely stromal thinning. A comparison of the breakpoints across all cases failed to reveal unique regions or genes in patients with CCO. CONCLUSIONS: 22q11.2 DS can rarely be associated with CCO. We describe a consistent pattern of central clearing related to posterior stromal thinning, with or without ICA/KLA. Possible candidate genes for corneal opacification in 22q11.2 DS remain elusive.

Congenital corneal staphyloma in 8q21.11 microdeletion syndrome.

BACKGROUND: Although 8q21.11 microdeletion syndrome (8q21.11 DS) has been reported in association with congenital corneal opacities, reports of the clinicopathological features and management are scarce. METHODS: We reviewed medical records including ophthalmic evaluations, imaging, operative reports, and pathology reports of two unrelated patients referred to the Ophthalmology Clinic of UPMC Children's Hospital of Pittsburgh with a cytogenetic diagnosis of 8q21.11 DS. RESULTS: Ophthalmological evaluation of both children revealed bilateral enlarged, staphylomatous, and cloudy corneas with neovascularization. These findings were consistent with the diagnosis of congenital corneal staphyloma (CCS). In one patient, anterior segment optical coherence tomography and high-frequency ultrasound revealed materials consistent with lens remnants embedded in the cornea; this was confirmed by histopathology. In the second patient, lens was found to be adherent to the cornea during surgery. One eye underwent enucleation for corneal perforation secondary to elevated intraocular pressure. In the other eyes, treatment consisted of penetrating keratoplasty combined with vitrectomy. Ahmed tube was subsequently placed to control intraocular pressure. CONCLUSION: 8q21.11 microdeletion syndrome can be associated with bilateral CCS, likely related to a combination of anterior segment developmental anomalies and elevated intraocular pressure. Tectonic penetrating keratoplasty is necessary to prevent corneal perforation, together with a strict control of the intraocular pressure.