Barrantes PC, Zhou P, MacDonald SM, Ioakeim-Ioannidou M, Lee NG. Granular Cell Tumor of the Orbit: Review of the Literature and a Proposed Treatment Modality. Ophthalmic Plast Reconstr Surg 2022;38(2):122-131.Abstract
PURPOSE: To document a unique case of granular cell tumor of the orbit, located lateral to and abutting the optic nerve, that benefited from treatment with proton beam irradiation, with a comprehensive review of the literature on granular cell tumor of the orbit. METHODS: Clinicopathologic case report with detailed imaging features and histopathologic and immunohistochemical evaluation for cytoplasmic tumor biomarkers differentiating granular cell tumor (GCT) from it mimicking lesions with relevant literature citations. The authors reviewed 20 cases of orbital GCT from 2011 to 2020 in addition to 40 cases from 1948 to 2011 and included a summary of imaging and clinical features, outcomes, and recommended treatment modalities. RESULTS: A 32-year-old man with 1-year history of left retrobulbar pain and diplopia on lateral gaze, intermittent left eyelid swelling, and a tonic left pupil was found to have a fusiform intraconal mass extending toward the orbital apex and abutting the optic nerve. Histopathologic and immunohistochemical investigations collectively supplied data diagnostic of a GCT with an initial low proliferation rate. GCT is a soft tissue neoplasm that originates in the nervous system and can occur anywhere in the body. This enhancing tumor is isointense to gray matter on T1-weighted MRI, hypointense on T2. After an incisional biopsy, the patient's symptoms persisted, and follow-up imaging several months later revealed further growth of the mass. The impossibility of complete surgical removal prompted the decision to treat with proton beam radiation therapy, which resulted in substantial regression in the size of the residual tumor. Most frequently involving the inferior rectus muscle (42%), orbital GCT is usually benign with only 4 reported cases of malignant orbital GCT (7%). Wide surgical resection with complete removal is usually curative for benign orbital GCT, and proton beam radiation therapy can aid in tumor shrinkage. CONCLUSIONS: GCT should be considered in the differential diagnosis when encountering patients with mass lesions involving the extraocular muscles, peripheral nerves, or less frequently, the optic nerve or orbital apex. Immunohistochemical analysis of biopsied tissue is required for the definitive diagnosis of GCT. Consideration of adjuvant therapies such as proton beam radiation therapy may be appropriate in cases of incomplete surgical resection of benign GCT. Proton beam radiation therapy can be an excellent therapeutic option for symptomatic relief and residual tumor size reduction with an acceptable toxicity profile.
Bresler SC, Simon C, Shields CL, McHugh JB, Stagner AM, Patel RM. Conjunctival Melanocytic Lesions. Arch Pathol Lab Med 2022;146(5):632-646.Abstract
CONTEXT.—: Conjunctival melanocytic lesions consist of a variety of neoplastic and nonneoplastic conditions. These include benign processes such as primary intraepithelial hypermelanosis and melanocytic hyperplasia, secondary forms of intraepithelial hypermelanosis and melanocytic hyperplasia, melanocytic nevi, melanocytic proliferations with malignant potential, and melanoma. OBJECTIVE.—: To provide a concise yet comprehensive resource regarding the histopathologic diagnosis of conjunctival melanocytic lesions. We aim to detail and clarify the numerous classification schemes that exist for junctional melanocytic proliferations of the conjunctiva (known as primary acquired melanosis or PAM; also termed conjunctival melanocytic intraepithelial neoplasia or C-MIN). Although not uniformly adopted, C-MIN is classified by using a numeric system based on a defined set of criteria. A less complex scheme (conjunctival melanocytic intraepithelial lesion or CMIL) has recently been proposed by the World Health Organization. Additionally, we aim to update the reader regarding molecular features and prognostic indicators. DATA SOURCES.—: Peer-reviewed literature and archived cases for illustration. CONCLUSIONS.—: Accurate histologic classification is essential, as PAM/C-MIN/CMILs that have a significant potential to progress to invasive melanoma may be clinically indistinguishable from low-risk lesions. Conjunctival melanoma (CM) more closely resembles cutaneous melanoma in terms of its pathogenesis and molecular features, compared to melanoma arising at other mucosal sites or to uveal melanoma. Depth of invasion and ulceration status, among other factors, have emerged as important prognostic indicators in CM. Sentinel lymph node biopsy may provide further prognostic information. Lastly, integration of pathologic and clinical findings is essential at this anatomically sensitive location to determine appropriate clinical management.
Baskaran M, Kumar RS, Friedman DS, Lu Q-S, Wong H-T, Chew PT, Lavanya R, Narayanaswamy A, Perera SA, Foster PJ, Aung T. The Singapore Asymptomatic Narrow Angles Laser Iridotomy Study: Five-Year Results of a Randomized Controlled Trial. Ophthalmology 2022;129(2):147-158.Abstract
PURPOSE: To examine the efficacy of laser peripheral iridotomy (LPI) in patients who received a diagnosis of primary angle-closure suspect (PACS). DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: This multicenter, randomized controlled trial ( identifier, NCT00347178) enrolled 480 patients older than 50 years from glaucoma clinics in Singapore with bilateral asymptomatic PACS (defined as having ≥2 quadrants of appositional angle closure on gonioscopy). METHODS: Each participant underwent prophylactic LPI in 1 randomly selected eye, whereas the fellow eye served as a control. Patients were followed up yearly for 5 years. MAIN OUTCOME MEASURES: The primary outcome measure was development of primary angle closure (PAC; defined as presence of peripheral anterior synechiae, intraocular pressure [IOP] of >21 mmHg, or both or acute angle closure [AAC]) or primary angle-closure glaucoma (PACG) over 5 years. RESULTS: Of the 480 randomized participants, most were Chinese (92.7%) and were women (75.8%) with mean age of 62.8 ± 6.9 years. Eyes treated with LPI reached the end point less frequently after 5 years (n = 24 [5.0%]; incidence rate [IR], 11.65 per 1000 eye-years) compared with control eyes (n = 45 [9.4%]; IR, 21.84 per 1000 eye-years; P = 0.001). The adjusted hazard ratio (HR) for progression to PAC was 0.55 (95% confidence interval [CI], 0.37-0.83; P = 0.004) in LPI-treated eyes compared with control eyes. Older participants (per year; HR, 1.06; 95% CI, 1.03-1.10; P < 0.001) and eyes with higher baseline IOP (per millimeter of mercury; HR, 1.35; 95% CI, 1.22-1.50; P < 0.0001) were more likely to reach an end point. The number needed to treat to prevent an end point was 22 (95% CI, 12.8-57.5). CONCLUSIONS: In patients with bilateral asymptomatic PACS, eyes that underwent prophylactic LPI reached significantly fewer end points compared with control eyes over 5 years. However, the overall incidence of PAC or PACG was low.
Heidary G, Aakalu VK, Binenbaum G, Chang MY, Morrison DG, VanderVeen DK, Lambert SR, Trivedi RH, Galvin JA, Pineles SL. Adjustable Sutures in the Treatment of Strabismus: A Report by the American Academy of Ophthalmology. Ophthalmology 2022;129(1):100-109.Abstract
PURPOSE: To review the scientific literature that evaluates the effectiveness of adjustable sutures in the management of strabismus for adult and pediatric patients. METHODS: Literature searches were performed in the PubMed database through April 2021 with no date limitations and were restricted to publications in English. The searches identified 551 relevant citations, of which 55 were reviewed in full text. Of these, 17 articles met the inclusion criteria and were assigned a level of evidence rating by the panel methodologist. The search included all randomized controlled studies regardless of study size and cohort studies of 100 or more patients comparing the adjustable versus nonadjustable suture technique, with a focus on motor alignment outcomes or reoperation rates. RESULTS: The literature search yielded no level I studies. Of the 17 articles that met the inclusion criteria, 11 were rated level II and 6 were rated level III. Among the 12 studies that focused on motor alignment outcomes, 4 small randomized clinical trials (RCTs) did not find a statistically significant difference between groups, although they were powered to detect only very large differences. Seven of 8 nonrandomized studies found a statistically significant difference in motor alignment success in favor of the adjustable suture technique, both overall and in certain subgroups of patients. Successful motor alignment was seen in both exotropia (in 3 studies that were not limited to children) and esotropia (in 1 study of adults and 2 of children). The majority of included studies that reported on reoperation rates found the rates to be lower in patients who underwent strabismus surgery with adjustable sutures, but this finding was not uniformly demonstrated. CONCLUSIONS: Although there are no level I studies evaluating the effectiveness of adjustable sutures for strabismus surgery, the majority of nonrandomized studies that met the inclusion criteria for this assessment reported an advantage of the adjustable suture technique over the nonadjustable technique with respect to motor alignment outcomes. This finding was not uniformly demonstrated among all studies reviewed and warrants further investigation in the development and analysis of adjustable suture techniques.
Hanyuda A, Rosner BA, Wiggs JL, Willett WC, Tsubota K, Pasquale LR, Kang JH. Prospective study of dietary intake of branched-chain amino acids and the risk of primary open-angle glaucoma. Acta Ophthalmol 2022;100(3):e760-e769.Abstract
PURPOSE: Metabolomic and preclinical studies suggest that branched-chain amino acids (BCAA) may be inversely associated with neurodegenerative diseases including glaucoma. We therefore assessed the long-term association between dietary intake of BCAA and incident primary open-angle glaucoma (POAG) and POAG subtypes. METHODS: We followed biennially participants of the Nurses' Health Study (NHS; 65 531 women: 1984-2016), Health Professionals Follow-up Study (42 254 men: 1986-2016) and NHSII (66 904 women; 1991-2017). Eligible participants were 40+ years old and reported eye examinations. Repeated validated food frequency questionnaires were used to assess dietary intake of BCAA. Incident cases of POAG and POAG subtypes defined by visual field (VF) loss and untreated intraocular pressure (IOP) were confirmed by medical record review. Multivariable-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: We identified 1946 incident POAG cases. The pooled MVRRs of POAG for the highest quintile (Q5 = 17.1 g/day) versus lowest quintile (Q1 = 11.2 g/day) of total BCAA intake was 0.93 (95% CI, 0.73-1.19; ptrend  = 0.45; pheterogeneity by sex  = 0.24). For subtypes of POAG defined by IOP level or POAG with only peripheral VF loss, no associations were observed for men or women (ptrend  ≥ 0.20); however, for the POAG subtype with early paracentral VF loss, there was a suggestion of an inverse association in women (MVRRQ5versusQ1  = 0.80 [95% CI, 0.57-1.12; ptrend  = 0.12]) but not in men (MVRRQ5versusQ1  = 1.38 [95% CI, 0.81-2.34; ptrend  = 0.28; pheterogeneity by sex  = 0.06]). CONCLUSION: Higher dietary intake of BCAA was not associated with POAG risk.
He B, Tanya SM, Wang C, Kezouh A, Torun N, Ing E. The Incidence of Sympathetic Ophthalmia After Trauma: A Meta-analysis. Am J Ophthalmol 2022;234:117-125.Abstract
PURPOSE: Sympathetic ophthalmia (SO) is a rare, bilateral panuveitis that occurs following open globe injury (OGI), with a variable incidence reported in the literature. Our objective was to determine the incidence proportion and incidence rate of SO following OGI to help guide shared physician-patient decision making. DESIGN: Systematic review and meta-analysis. METHODS: A systematic literature search was performed using the MEDLINE, EMBASE, and Cochrane databases from inception to November 2020 for population-based studies on OGI and SO in adults and children. Two reviewers independently screened search results. Random-effects meta-analyses were performed to calculate the incidence proportion and incidence rate. The Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool was used to assess the risk of bias. The study was registered on PROSPERO CRD42020198920. RESULTS: A total of 24 studies were utilized in the meta-analyses. After OGI, the estimated overall incidence proportion of SO was 0.19% (95% CI 0.14%-0.24%) and the incidence rate of SO was 33 per 100,000 person-years, (95% CI 19.61-56.64) with I2 of 13% and 72%, respectively. CONCLUSIONS: SO after OGI is rare. The estimated incidence proportion and incidence rate are useful when counselling patients regarding management options after OGI. Further studies are needed to examine the influence of age, the extent and location of trauma, timing of repair, and prophylactic eye removal on the incidence of SO.
Oke I, Elhusseiny AM, Shah AS, Hunter DG. Botulinum Toxin Injection of the Inferior Oblique Muscles for V-Pattern Strabismus and Primary Position Hypertropia. Am J Ophthalmol 2022;235:32-37.Abstract
PURPOSE: To evaluate outcomes of botulinum toxin (BTX) injection of the inferior oblique (IO) muscle. DESIGN: Retrospective case series. METHODS: Setting: Single center, ophthalmology department at Boston Children's Hospital. STUDY POPULATION: All patients treated with IO muscle injection of BTX (onabotulinumtoxinA) between 2010 and 2020. OBSERVATION PROCEDURE: Sensorimotor evaluations at short-term (<2 months), medium-term (2-4 months), and long-term (≥4 months) intervals. OUTCOME MEASURE: Primary outcomes included median improvement in V-pattern strabismus and primary position hypertropia. Secondary outcomes included IO muscle overaction. Wilcoxon signed-rank tests were performed to identify differences before and after injection. RESULTS: Record review identified 20 patients with a median age of 4.5 (range, 1-69) years. Median BTX dose injected (31 IO muscles) was 5.0 (range, 3.0-7.0) units. Indications included V-pattern strabismus (N = 8), hypertropia (N = 7), or both (N = 5). Median long-term interval was 6.4 (range, 4.1-26.6) months. Injections were concurrent with treatment of horizontal strabismus in all but 3 cases. Median V-pattern magnitude changed from 10 prism diopters (PD) preoperatively to 0 PD short-term (P = .006) and 3.5 PD long-term (P = .34). Median hypertropia changed from 8.5 PD preoperatively to 1.5 PD short-term (P = .01) and 8 PD long-term (P = .87). Median IO muscle overaction grade improved significantly at short-term (P < .001) and long-term (P = .007) intervals. There were no complications associated with the IO muscle injections. CONCLUSIONS: BTX injection of the IO muscles can be a useful adjunct to the management of V-pattern strabismus. Intervention for primary position hypertropia may be helpful for short-term relief with no expectation of long-term benefit.
Kretz AM, Vongsachang H, Friedman DS, Callan J, Wahl M, Mukherjee RM, Neitzel A, Collins ME. Stakeholders' Perceptions of a School-Based Eye Care Programme in Baltimore, MD. Ophthalmic Epidemiol 2022;29(3):252-261.Abstract
PURPOSE: To explore stakeholders' perceptions of a school-based vision programme (SBVP). METHODS: We conducted 20 focus groups with 105 parents and teachers at schools in Baltimore, MD, that participated in a SBVP. Facilitators used a semi-structured interview guide to discuss participants' perceptions of the SBVP. Focus groups were audio-recorded, transcribed, and coded using inductive thematic analysis. RESULTS: Participant perceptions fell into three categories: benefits of school-based eye care, limitations of school-based eye care, and observation of impact. The majority of participants had positive comments about the programme; benefits included convenience (location, time, and cost), the comprehensive nature of the programme, the quality of the eyeglasses and ability to receive replacements, and a positive screening/exam experience. Limitations of programme impact were related to communication and organisation, the time to receive the glasses, missed instructional time, and uncertainty about screenings. Observations of impact included academic and classroom improvements, as well as visual and other health improvements. CONCLUSION: Parents and teachers reported mostly positive perceptions regarding the SBVP. Their appreciation for the convenience underscores that location, cost, time, and comprehensive services are crucial aspects for implementing a successful programme. To maximize impact, programs must also implement robust communication campaigns that integrate into the schools' workflow to help parents and teachers stay engaged in the process from start to finish.
Català P, Thuret G, Skottman H, Mehta JS, Parekh M, Ní Dhubhghaill S, Collin RWJ, Nuijts RMMA, Ferrari S, LaPointe VLS, Dickman MM. Approaches for corneal endothelium regenerative medicine. Prog Retin Eye Res 2022;87:100987.Abstract
The state of the art therapy for treating corneal endothelial disease is transplantation. Advances in the reproducibility and accessibility of surgical techniques are increasing the number of corneal transplants, thereby causing a global deficit of donor corneas and leaving 12.7 million patients with addressable visual impairment. Approaches to regenerate the corneal endothelium offer a solution to the current tissue scarcity and a treatment to those in need. Methods for generating corneal endothelial cells into numbers that could address the current tissue shortage and the possible strategies used to deliver them have now become a therapeutic reality with clinical trials taking place in Japan, Singapore and Mexico. Nevertheless, there is still a long way before such therapies are approved by regulatory bodies and become clinical practice. Moreover, acellular corneal endothelial graft equivalents and certain drugs could provide a treatment option for specific disease conditions without the need of donor tissue or cells. Finally, with the emergence of gene modulation therapies to treat corneal endothelial disease, it would be possible to treat presymptomatic patients or those presenting early symptoms, drastically reducing the need for donor tissue. It is necessary to understand the most recent developments in this rapidly evolving field to know which conditions could be treated with which approach. This article provides an overview of the current and developing regenerative medicine therapies to treat corneal endothelial disease and provides the necessary guidance and understanding towards the treatment of corneal endothelial disease.
Chinn RN, Michalak SM, Shoshany TN, Bishop K, Staffa SJ, Hunter DG. Effect of Sequential and Simultaneous Patching Regimens in Unilateral Amblyopia. Am J Ophthalmol 2022;233:48-56.Abstract
PURPOSE: Many clinicians treat unilateral amblyopia with glasses alone and initiate patching when needed; others start glasses and patching simultaneously. In this study, we reviewed the outcomes of the two approaches at our institution. DESIGN: Retrospective nonrandomized clinical trial. METHODS: Setting: Institutional practice. PATIENT POPULATION: All patients diagnosed with amblyopia at Boston Children's Hospital between 2010 and 2014. INCLUSION CRITERIA: Unilateral amblyopia (visual acuity (VA) 20/40 to 20/200 with interocular difference ≥3 lines,) age 3 to 12 years, with a 6-month follow-up visit. EXCLUSION CRITERIA: Deprivation amblyopia, prior amblyopia treatment, treatment other than patching, surgery. Patients were categorized as "simultaneous treatment" (concurrent glasses and patching therapy at their first visit) or "sequential treatment" (glasses alone at first visit, followed by patching therapy at second visit.) Observation procedures: Patient demographics, VA, and stereopsis were compared. OUTCOME MEASURES: VA and stereopsis at the last visit on treatment. RESULTS: We identified 98 patients who met inclusion criteria: 36 received simultaneous treatment and 62 sequential treatment. Median amblyopic eye VA improved similarly between the simultaneous (∆0.40; interquartile range [IQR], 0.56-0.30 logMAR) and sequential (∆0.40; IQR, 0.52-0.27 logMAR) groups. Patients without stereopsis at first visit had better stereopsis outcomes with sequential treatment (5.12 [IQR, 4.00-7.51] log stereopsis) compared with simultaneous treatment (8.01 [IQR, 5.65-9.21]) log stereopsis, P = 0.046). CONCLUSIONS: VA improved approximately 4 lines regardless of treatment type. For children without stereopsis at first presentation, sequential patching yielded better stereopsis outcomes. These findings require further validation and highlight the importance of evaluating stereopsis in future studies.
Habib LA, North VS, Freitag SK, Yoon MK, Lefebvre DR, Lee NG. Medical comorbidities and orbital implant exposure. Acta Ophthalmol 2022;100(3):e813-e819.Abstract
PURPOSE: To investigate medical conditions and systemic therapies associated with orbital implant exposure in patients with anophthalmic sockets. METHODS: Retrospective review of patients who underwent enucleation or evisceration at a single centre between January 1, 2008 and March 1, 2018. Medical comorbidities, including peripheral or coronary artery disease, rheumatologic conditions, diabetes, malignancy and history of smoking were recorded. Use of immunomodulatory and anticoagulation therapy at the time of eye removal was noted. Patients were divided into two groups-those with implant exposure and those without. Univariate and multivariate analysis was used to compare groups. RESULTS: Two hundred and twenty-nine patients underwent eye removal surgery over a ten-year period. Implant exposure was seen in 20 (8.7%) patients. Univariate analysis revealed a statistically significant difference between groups in rates of smoking, malignancy, and immunomodulatory therapy at the time of surgery. A history of smoking (HR = 11.72; 95% CI: 2.95, 46.53; p = 0.0001) and immunomodulatory therapy (HR = 8.02; 95% CI: 1.96, 32.87; p = 0.004) were independent predictors of exposure. The probability of exposure was 81.2% when all three risk factors were present versus 4.4% when none were present (c-index = 0.737, 95% CI: 0.608, 0.865; p < 0.001). The model was a good fit to the data (Hosmer-Lemeshow goodness-of-fit test p = 0.475). CONCLUSIONS: Smoking and immunomodulatory therapy were associated with orbital implant exposure in patients with anophthalmic sockets. This is the first report examining medical comorbidities in patients with orbital implant exposure. Understanding the pathophysiology of implant exposure is crucial to preoperative planning and postoperative care.
Neerukonda VK, Stagner AM, Wolkow N. Lymphoma of the Lacrimal Sac: The Massachusetts Eye and Ear Experience With a Comparison to the Previously Reported Literature. Ophthalmic Plast Reconstr Surg 2022;38(1):79-86.Abstract
PURPOSE: To describe the frequency, clinical features, and histologic subtypes of biopsy proven lacrimal sac lymphomas, and to compare these results to the previously published literature. METHODS: A retrospective chart review was performed at a single institution from 2004 to 2017. Pathology reports, operative notes, and patients' medical charts were reviewed. RESULTS: Of 566 lacrimal sacs submitted for routine histopathologic evaluation, 16 cases of lymphoma were identified. All were low-grade, non-Hodgkin B-cell lymphomas, biopsied at an average age of 71 years. Thirteen patients (81.25%) had a pre-existing lymphoma diagnosis; the average interval between the diagnosis of systemic or nonocular adnexal lymphoma and lacrimal sac lymphoma was 7.9 years (range 2-26 years; median 5.5 years). Three cases of primary lacrimal sac lymphoma were identified. Histopathology showed 3 cases (18.75%) of follicular lymphoma, 3 (18.75%) of extranodal marginal zone lymphoma, and 10 (62.5%) of chronic lymphocytic leukemia/small lymphocytic lymphoma. Primary cases presented with epiphora and nasolacrimal duct obstruction, while secondary cases predominantly manifested as dacryocystitis. All lacrimal sac neoplasms were locally responsive (without local recurrence) to chemotherapy, radiation, or both. CONCLUSIONS: Lacrimal sac lymphoma is uncommon but should be suspected among patients with known lymphoma who develop dacryocystitis. In this series, primary lacrimal sac lymphoma most often presented as a mass or nasolacrimal duct obstruction. Chronic lymphocytic leukemia/small lymphocytic lymphoma was the most commonly identified cause of secondary lacrimal sac lymphoma. Distinguishing primary from secondary lacrimal sac lymphomas is important, as the extent of disease and histopathologic subtypes differ, which may affect patient management.
Elhusseiny AM, Jabroun M, Rajabi F, Gonzalez E, Alkharashi M. A novel variant in the gene-presenting as unilateral myopia, pediatric cataract, and heterochromia in a patient with familial exudative vitreoretinopathy. Eur J Ophthalmol 2022;32(6):NP6-NP9.Abstract
PURPOSE: To report a case of 16-month-old boy with a novel variant TSPAN12 gene-presenting as unilateral myopia, pediatric cataract, and heterochromia in a patient with familial exudative vitreoretinopathy. OBSERVATION: A 16-month-old otherwise healthy boy was referred to Boston Children's Hospital for evaluation of strabismus. Ocular examination revealed intermittent esotropia, left hypotropia, and limited left eye elevation in both adduction and abduction. Full cycloplegic hyperopic correction of +3.50 diopters (D) over both eyes was given to the patient. Over several months, refraction of the right eye showed progressive myopia (-6.00 D) with new onset iris heterochromia. Fundus examination showed there was a large area of chorioretinal atrophy with abrupt ending of the blood vessels; anterior to the ora serrata there were diffuse vitreous bands and veils that reached the lens anteriorly in direct contact with the lenticular opacity. A novel heterozygous nonsense likely pathogenic variant was identified in the TSPAN12 gene (NM_012338.3) c.315T>A (p.Cys105Ter) confirming the diagnosis of FEVR. CONCLUSION AND IMPORTANCE: Asymmetric FEVR rarely present with unilateral axial myopia however association with acquired heterochromia and cataract has never been reported. We report a case of FEVR caused by a novel TSPAN12 likely pathogenic nonsense variant presenting as unilateral progressive myopia, acquired heterochromia, and pediatric cataract.