Four Unique Genetic Variants in Three Genes Account for 62.7% of Early-Onset Severe Retinal Dystrophy in Chile: Diagnostic and Therapeutic Consequences.

Leber congenital amaurosis (LCA)/early-onset severe retinal dystrophy (EOSRD) stand as primary causes of incurable childhood blindness. This study investigates the clinical and molecular architecture of syndromic and non-syndromic LCA/EOSRD within a Chilean cohort (67 patients/60 families). Leveraging panel sequencing, 95.5% detection was achieved, revealing 17 genes and 126 variants (32 unique). CRB1, LCA5, and RDH12 dominated (71.9%), with CRB1 being the most prevalent (43.8%). Notably, four unique variants (LCA5 p.Glu415*, CRB1 p.Ser1049Aspfs*40 and p.Cys948Tyr, RDH12 p.Leu99Ile) constituted 62.7% of all disease alleles, indicating their importance for targeted analysis in Chilean patients. This study underscores a high degree of inbreeding in Chilean families affected by pediatric retinal blindness, resulting in a limited mutation repertoire. Furthermore, it complements and reinforces earlier reports, indicating the involvement of ADAM9 and RP1 as uncommon causes of LCA/EOSRD. These data hold significant value for patient and family counseling, pharmaceutical industry endeavors in personalized medicine, and future enrolment in gene therapy-based treatments, particularly with ongoing trials (LCA5) or advancing preclinical developments (CRB1 and RDH12).

Clinical presentations and surgical outcomes of intraocular foreign body presenting to an ocular trauma unit.

OBJECTIVES: To describe, evaluate, and identify the characteristics, prognostic factors, and visual outcomes in patients with intraocular foreign body (IOFB) in a Latin American population. METHODS: A retrospective, observational case-series of patients with a diagnosis of IOFB. Variables analyzed included age, gender, initial and final best correct visual acuity (BCVA), ocular trauma score, intraocular pressure, mechanism of injury, material and number of IOFB, zone of injury, timing of primary repair and IOFB removal, complications, and follow up. RESULTS: Sixty-one patients with IOFB were identified of which 97% were male with a mean age of 37.9 years (SD 2.16). The most common IOFB location was intravitreal (43%). IOFBs were metallic in 78%, vegetal in 3%, and other materials in 11%. Primary repair and secondary IOFB removal were performed at a mean timepoint of 3 days and 5 days, respectively. Systemic and topical antibiotics were administered to all patients. The initial BCVA was 1.62 logMAR and the final was 0.6 logMAR, which was statistically significant (Pearson's chi-squared test, p value 0.01). No cases of endophthalmitis were seen. CONCLUSION: IOFB removal can be delayed when there are no signs of infection or evidence of retinal detachment, without an increased risk of endophthalmitis and a negative impact on visual outcomes. Use of topical and systemic antibiotics appear sufficient to prevent endophthalmitis in these cases.

Ophthalmic genetics in South America.

South America comprises of heterogeneous topographies, populations, and health care systems. Therefore, it is not surprising to see differences among the countries regarding expertise, education, and practices of ophthalmic genetics for patients with rare eye diseases. Nevertheless, common challenges such as limited genetics training in medical schools and among ophthalmologists, scarcity of diagnostic tools for phenotyping, and expensive genetic testing not covered by the public healthcare systems, are seen in all of them. Here, we provide a detailed report of the current status of ophthalmic genetics, described by the personal views of local ophthalmologists from Brazil, Colombia, Argentina, and Chile. By reporting our strengths and weaknesses as a region, we intend to highlight the need for guidelines on how to manage these patients aligned with public health policies. Our region contributes to research worldwide, with thousands of well diagnosed patients from a number of unique and genetically diverse populations. The constant expansion of ophthalmic genetics and molecular diagnostics requires us to join forces to collaborate across South America and with other countries to improve access to next-generation diagnostics and ultimately improve patient care.

A Study of the Natural History of Vitreomacular Traction Syndrome by OCT.

PURPOSE: To examine the natural history of vitreomacular traction syndrome (VMTS) in the absence of other ocular comorbidities. DESIGN: Retrospective clinical case series. PARTICIPANTS: A total of 183 eyes of 159 patients diagnosed with VMTS with no other ocular comorbidity. METHODS: Patients with VMTS were identified from an OCT database at Moorfields Eye Hospital, London. Sequential OCT scans and patient notes were reviewed over a minimum period of 6 months. Data collected included patient demographics, best-corrected visual acuity, and OCT features of vitreomacular adhesion. Contingency tests and binary logistic modeling were used to identify baseline predictors of stability and progression. MAIN OUTCOME MEASURES: The rates of spontaneous resolution (defined by release of traction), progression to full-thickness macular hole, and surgical intervention were analyzed. RESULTS: Presenting visual acuity was 0.3±0.3 logMAR units. The mean length of follow-up was 17.4±12.1 months. During this period, VMTS persisted in 60% and resolved in 20% (occurring on average at 15 months). Of the remainder, 12% developed a macular hole and 8% elected to proceed with surgery for symptoms. Focal adhesion <1500 µm was present in 87%. A premacular membrane with macular pucker (PMM) was present in 20%. With persistent VMTS, vision and central foveal thickness remained unchanged. The relative risk of resolution increased in those cases with better presenting visual acuities, lesser foveal thicknesses, and no associated PMMs; vision significantly improved in those cases with resolution. CONCLUSIONS: VMTS persists in the majority of patients but despite this, visual acuities did not deteriorate significantly over the study period unless patients developed a full-thickness macular hole or required surgical intervention for symptoms. Resolution spontaneously occurred in 20%, with an improvement in vision.

PRIMARY SCLERAL BUCKLING FOR PEDIATRIC RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate the anatomical outcomes of primary scleral buckling (SB) procedures for pediatric rhegmatogenous retinal detachments. METHODS: Retrospective consecutive case series. One hundred and four eyes of 99 consecutive nonselected pediatric patients undergoing primary SB were identified. Baseline factors recorded were demographics, presenting clinical examination findings, previous ocular surgery, predisposing factors. Intraoperative factors recorded were the type of buckle, number and distribution of retinal breaks, number of retinal quadrants detached, macular status (involved vs. uninvolved), the use of subretinal fluid drainage, and surgical complications. Anatomical reattachment rate at last follow-up. Subgroup analysis was carried out to identify any predisposing factors for failure of primary surgery, effect of age on outcome, intraoperative pathology, effect of posterior versus anterior SB, and redetachment and secondary-procedure complications specific to SB. RESULTS: The initial surgery was segmental SB alone in 87 eyes (83.6%). Retinal reattachment was achieved with 1 operation in 73% (76 of 104 eyes). Of the 28 cases that redetached, 14 eyes underwent a repeat SB procedure (success rate of this second operation: 85.7% [12 of 14 eyes]), 13 eyes underwent vitrectomy (success rate of this second operation: 38.4% [5 of 13 eyes]), and 1 case was not reoperated. Overall, the final success rate was 94% (98 of 104 eyes). Factors associated with a statistically significant increased risk of failure included more than one break; three or more quadrants of detachment; horseshoe tears; no breaks seen on preoperative examination; Stickler syndrome. CONCLUSION: In selected cases, primary SB is an effective treatment for pediatric, rhegmatogenous retinal detachment.

Clinical and Genetic Characterization of RDH12-Retinal Dystrophy in a South American Cohort.

PURPOSE: To characterize the largest cohort of individuals with retinol dehydrogenase 12 (RDH12)-retinal dystrophy to date, and the first one from South America. DESIGN: Retrospective multicenter international study. SUBJECTS: Seventy-eight patients (66 families) with an inherited retinal dystrophy and biallelic variants in RDH12. METHODS: Review of clinical notes, ophthalmic images, and molecular diagnosis. MAIN OUTCOME MEASURES: Visual function, retinal imaging, and characteristics were evaluated and correlated. RESULTS: Thirty-seven individuals self-identified as Latino (51%) and 34 as White (47%). Sixty-nine individuals (88%) had Leber congenital amaurosis (LCA)/early-onset severe retinal dystrophy. Macular and midperipheral atrophy were seen in all patients from 3 years of age. A novel retinal finding was a hyperautofluorescent ring in 2 young children with LCA. Thirty-nine patients (50%) had subsequent visits, with mean follow-up of 6.8 ± 7.3 (range, 0-29) years. Eight variants (21%) were previously unreported, and the most frequent variant was c.295C>A, p.Leu99Ile, present in 52 alleles of 32 probands. Individuals with LCA homozygous for p.Leu99Ile (31%) had a later age of onset, a slower rate of best-corrected visual acuity decrease, the largest percentage of patients with mild visual impairment, and were predicted to reach legal blindness at an older age than the rest of the cohort. CONCLUSIONS: By describing the largest molecularly confirmed cohort to date, improved understanding of disease progression was possible. Our detailed characterization aims to support research and the development of novel therapies that may have the potential to reduce or prevent vision loss in individuals with RDH12-associated retinal dystrophy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures.

Clinical, histopathological, and genetic aspects in one case of ligneous conjunctivitis.

Ligneous conjunctivitis is an uncommon and recurrent type of chronic conjunctivitis. A prevalent cause of this disease is a Plasminogen deficiency, resulting from recessive mutations in the human encoding plasminogen (PLG) gene. This deficiency affects the conjunctiva and also other mucous membranes. Only few hundred cases have been reported in the literature. Here we report a case of a 9-year-old boy with diagnosis of ligneous conjunctivitis. Histopathological examination in hematoxylin-eosin (HE) staining and sequencing of PLG gene were performed to confirm diagnosis. Histopathological findings confirmed the diagnosis of ligneous conjunctivitis. The patient is compound heterozygous for c.1026T>G (p.Val342Gly) and c.2384G>C (p.Arg795Pro) mutations in PLG gene. Both mutations have not been described previously, and the bioinformatic analysis strongly suggests that are causative of the disease. To the best of our knowledge, this is the first case report of a Chilean patient with ligneous conjunctivitis.

Long-Term Survival Rates of Patients Undergoing Vitrectomy for Proliferative Diabetic Retinopathy.

PURPOSE: Reported 5-year survival rates in patients undergoing vitreous surgery for proliferative diabetic retinopathy (PDR) range from 68-95%. Studies relating survival rates to medical baseline characteristics predate the millennium. This study aimed to update data on life expectancy of patients undergoing vitrectomy for PDR and identify baseline factors which may influence survival. METHODS: A retrospective cohort study of consecutive patients who underwent their first pars-plana vitrectomy for PDR between April 2004 and May 2005 was performed. Survival status on 1 May 2012 was the primary endpoint. The Kaplan-Meier life table method was used to determine survival rates. Univariate and multiple variable Cox proportional hazards regressions were used to identify risk factors for mortality. RESULTS: A total of 148 patients were included in the study, with a mean age of 54 years (range 20-80 years) at time of surgery. The 3-, 5- and 7-year survival rates were 94%, 86% and 77%, respectively (95% confidence interval, CI, 88-97%, 79-91% and 68-84%, respectively). Renal failure was the most common cause of death. The presence of limb ulcers at baseline was the most important prognostic indicator for mortality, with a hazard ratio of 3.13 (95% CI 1.46-6.71, p = 0.003) and a survival rate at 5 years reduced to 79%. CONCLUSION: The 5-year survival rate remains comparable to those reported 20 years ago despite a lowering in threshold for vitrectomy and increased health awareness. Limb ulcers are strongly associated with increasing mortality. Clinicians should remain mindful of the systemic associations of diabetes particularly in advanced retinal disease.