Spectrum of variants associated with inherited retinal dystrophies in Northeast Mexico.

BACKGROUND: Inherited retinal dystrophies are hereditary diseases which have in common the progressive degeneration of photoreceptors. They are a group of diseases with clinical, genetic, and allelic heterogeneity. There is limited information regarding the genetic landscape of inherited retinal diseases in Mexico, therefore, the present study was conducted in the northeast region of the country. METHODS: Patients with inherited retinal dystrophies were included. A complete history, full ophthalmological and medical genetics evaluations, and genetic analysis through a targeted NGS panel for inherited retinal dystrophies comprising at least 293 genes were undertaken. RESULTS: A total of 126 patients were included. Cases were solved in 74.6% of the study's population. Retinitis pigmentosa accounted for the most found inherited retinal disease. Ninety-nine causal variants were found, being USH2A and ABCA4 the most affected genes (26 and 15 cases, respectively). CONCLUSIONS: The present study documents the most prevalent causative genes in IRDs, as USH2A, in northeastern Mexico. This contrasts with previous reports of IRDs in other zones of the country. Further studies, targeting previously unstudied populations in Mexico are important to document the genetic background of inherited retinal dystrophies in the country.

Selective laser trabeculoplasty is safe and effective in patients previously treated with prostaglandin analogs: An evidence-based review.

PURPOSE: Prostaglandin analogs (PGAs) are first-line treatments for ocular hypertension (OHT) and open-angle glaucoma (OAG). However, frequent side effects and high costs hinder patient's compliance resulting in disease progression. Evidence suggests selective laser trabeculoplasty (SLT) may be considered a first-line treatment for OHT and OAG due to its safety profile, minor side effects, and reduced costs. Considering that PGAs and SLT share action mechanisms, it is hypothesized that previous PGA therapy may affect subsequent SLT efficacy. Therefore, we analyzed if PGAs reduce SLT efficacy. METHODS: An evidence-based review was performed to assess the safety and efficacy of SLT in patients previously treated with PGAs. For this purpose, we performed an extensive literature search using the National Library of Medicine's PubMed and Google Scholar database for all English language articles published until May 2021. RESULTS: There is evidence of non-superiority of PGAs therapy versus SLT for OHT and OAG. A multicenter, randomized, observer-masked clinical trial (RCT) of untreated OHT and OAG patients concluded that SLT should be offered as the first-line treatment for these patients. This study was supported by a meta-analysis of RCTs, comparing SLT efficacy versus antiglaucoma drugs only, with the advantage of an SLT lower rate of adverse effects. CONCLUSIONS: Cost-effectiveness, patient compliance, and antiglaucoma drugs' side effects, including higher surgical failure, favor consideration of SLT as first-line therapy for OAG and OHT. Furthermore, SLT efficacy does not seem to be affected by prior PGA administration; however, larger cohort, comparative, multicenter RCTs are necessary to answer this question.

Clinical profile of melanocytic lesions of the ocular surface in a Hispanic population.

PURPOSE: To determine the prevalence, clinical characteristics, and demographic factors of melanocytic lesions of the ocular surface, such as racial melanosis, primarily acquired melanosis, conjunctival nevus, and conjunctival melanoma in a Hispanic population. MATERIALS AND METHODS: A cross-sectional and observational study was undertaken in a tertiary referral ophthalmological center in northern Mexico from December 2020 to April 2021. All patients attending an ophthalmology specialty clinic were screened during their first visit in order to detect melanocytic lesions of the ocular surface. Demographic factors, clinical characteristics, and diagnosis and treatment were recorded. RESULTS: 227 patients were screened for melanocytic lesions. Melanocytic lesions were identified in 114 patients (50.2%). The prevalence of the different melanocytic lesions in the screened population was racial melanosis, 45.3%; primary acquired melanosis, 3.5%, and conjunctival nevus 1.3%. No conjunctival melanoma was identified in the screened population. Primary acquired melanosis was more common in the fifth to sixth decade of life and in females. Racial melanosis showed no gender predilection and was also more common in the fifth to sixth decade of life. Only 1 melanocytic lesion (a primary acquired melanosis) required medical treatment with excisional biopsy and cryotherapy. CONCLUSION: The prevalence of racial melanosis is remarkably high in the Hispanic population. While less prevalent, primary acquired melanosis is also present in a considerable percentage of Hispanic patients. Both melanocytic lesions exhibit demographic characteristics that match those previously reported in the medical literature.

Ocular involvement and complications of lichen planus, lichen planus pigmentosus, and lichen planopilaris: A comprehensive review.

Ocular involvement of lichenoid dermatoses, such as lichen planus (LP), lichen planus pigmentosus (LPP), and lichen planopilaris (LPL), although uncommon, is associated with skin manifestations. Isolated ocular involvement is very rare. When lesions are confined to the skin, the dermatologist inquires and evaluates for oral and genital symptoms and lesions, respectively; hence, eye manifestations are commonly neglected by the non-ophthalmologist. Ocular involvement in LP, LPP, and LPL may result in significant morbidity. An ophthalmic interrogatory and a gross ophthalmic evaluation performed by the dermatologist may unravel ocular signs and symptoms that require evaluation by an eye specialist. Ocular surface inflammation and scarring, when untreated, results in serious complications such as corneal perforation and permanent vision loss. This review aims to present an up-to-date overview for the dermatologist of the ocular involvement and complications of LP, LPP, and LPL, and when to refer to the ophthalmologist to prevent blinding complications.

Isotretinoin and the eye: A review for the dermatologist.

Due to the prevalence of acne vulgaris, isotretinoin is one of the most prescribed drugs among physicians and dermatologists. Although exhibiting an adequate safety profile, adverse events secondary to isotretinoin use are common. Before prescribing isotretinoin, physicians usually inquire about pregnancy and perform serologic tests including cholesterol, triglycerides, and liver enzymes. Ocular manifestations are commonly neglected. Despite being generally mild, ocular manifestations related to either topical or systemic isotretinoin may cause important ocular morbidity. The ocular surface is the most affected site within the eye; however, retinal and optic nerve disease also have been documented. Evaporative dry eye disease, which may range from mild to severe, is the most common adverse ocular effect associated with isotretinoin use. The aim of this review is to present an up-to-date overview for the dermatologist about the prevention, diagnosis, and treatment of the ocular side effects of isotretinoin, and when to refer to the eye specialist.

Multimodal and longitudinal evaluation of novel phenotype-genotype correlation of CLN3 isolated retinal degeneration in an hispanic female with heterozygous mutations c.944dup and c.1305C>G.

BACKGROUND: Inherited retinal disorders (IRDs) are a complex group of heritable diseases which are characterized by rod, cone, retinal pigment epithelium, or optic nerve dysfunction. Recently, mutations in CLN3 have also been associated with isolated IRDs. Herein, a case with heterozygous CLN3 variations that had not been previously linked to a CLN3-isolated retinal degeneration (CLN3IRD) phenotype in a Hispanic female and its multimodal imaging findings across a 10-year follow-up are presented. MATERIAL AND METHODS: An observational, prospective, case report on a hispanic female with CLN3IRD is presented. Patients underwent genetic testing and color fundus photography (CFC) and autofluorescence (FAF), fluorescein angiography (FA), Spectral domain optical coherence tomography (OCT) of the macular area, electroretinogram (ERG) and 30-2 visual field examination through automated perimetry. RESULTS: A female, aged 24, affected by CLN3IRD phenotype from c.944dup and c.1305C>G compound heterozygous variants, presented with bilateral hypopigmentary changes in the macular area of OU with that corresponded to hyporautofluorescent deposits in the macular area on FAF. An atrophic maculopathy was evident on structural OCT, and FA disclosed a symmetrical macular hyperflourescence with staining in the early and late stages in OU. Humphrey visual field testing showed a marked reduction of the central visual field in OU. Electrophysiological testing revealed an ERG with markedly decreased a and b waves in OU. In ten years follow up developed of bone spiculae in the midperipheral retina. CONCLUSIONS: We reported a patient with a novel CLN3IRD severe phenotype associated with the variants c.944dup and c.1305C>G, which had previously only been associated with JCNL.

Challenges in the diagnosis and management of simultaneous, bilateral, toxic anterior segment syndrome after phacorefractive surgery.

A 59-year-old woman presented with a 24-hour history of severe, bilateral, painless vision loss starting 1 day after immediately sequential, bilateral, phacorefractive surgery with multifocal intraocular lens (IOL) implantation at another institution. Best-corrected visual acuity was counting fingers at 1 foot in the right eye and 20/100 in the left eye. Slit-lamp evaluation showed a dense fibrin membrane on the anterior surface of the IOL and significant anterior chamber inflammation in both eyes. B-scan ultrasound revealed bilateral vitreous haze, without membrane formation. The rapid onset, absence of sharp pain, ciliary injection, conjunctival chemosis, eyelid edema, and erythema raised suspicion for bilateral toxic anterior segment syndrome. Significant clinical improvement after high-dose prednisone and hourly prednisolone acetate eye drops supported the diagnosis. After 6 months of tapering anti-inflammatory therapy, optical coherence tomography of the macula showed no pathologic changes, and the patient's best-corrected visual acuity improved to 20/25 in both eyes.

Rheumatoid arthritis-associated peripheral ulcerative keratitis outcomes after early immunosuppressive therapy.

BACKGROUND/AIMS: To evaluate the role of early immunosuppressive therapy (IMT) in the management of rheumatoid arthritis (RA)-associated peripheral ulcerative keratitis (PUK). METHODS: Single-centre, retrospective, comparative cohort study. Patients with RA-associated PUK were divided into two groups; those exposed to and those not exposed to early IMT, defined as administrating therapy within the first 4 weeks from the PUK onset. Outcomes included PUK recurrence, control of inflammation and development of ocular complications, including corneal scarring and perforation, cataract formation or progression and permanent visual loss. RESULTS: A total of 52 eyes from 36 patients were included for analysis; 37 (71.2%) eyes received early IMT and 15 (28.8%) eyes did not. Follow-up time was 41.2+53.3 months (range: 4-236 months). While early IMT was a protective factor (HR 0.345, 95% CI 0.126 to 0.946, p=0.039), late RA diagnosis after PUK onset (HR 4.93, 95% CI 1.75 to 13.85, p=0.002) and retarded (≥2 months) control of inflammation (HR 8.37, 95% CI 1.88 to 37.16, p=0.005) were risk factors for PUK recurrence. Late IMT (OR 7.75, 95% CI 2.00 to 29.99, p=0.003), an unknown diagnosis of RA at first visit (OR 4.14, 95% CI 1.15 to 14.91, p=0.030) and at least one PUK recurrence (OR 6.42, 95% CI 1.71 to 24.07, p=0.006) were risk factors for visual loss. Survival analysis rendered eyes exposed to early IMT a lower risk of PUK recurrence (p=0.039). CONCLUSION: Eyes with RA-associated PUK exposed to early IMT were more likely to achieve earlier inflammatory control, fewer recurrences and had better visual outcomes.

Retinoblastoma in an older Hispanic child masquerading as pars planitis: A case report.

INTRODUCTION: To report a case of a Hispanic girl with late-onset Retinoblastoma (Rb) who was misdiagnosed as a pars planitis prior to referral. Nearly 95% of all Rb cases are detected before age 5, and this patient was 8 years-old. METHODS: Case report of a late-onset Retinoblastoma with anterior chamber (AC) involvement plus the presence of an Ahmed valve. The patient had a history of a couple of months of topical therapy comprising medication for glaucoma, systemic steroids, and a filtration surgery (Ahmed valve), after that a biopsy was performed prior to referral. Upon arrival at our clinic, we performed an examination under anesthesia (EUA) and a B-scan ultrasound (US). RESULTS: Unilateral Retinoblastoma with an Ahmed valve in an AC filled with Rb seeds was diagnosed with the EUA and US in the left eye. An orbital exenteration with map biopsies of the left orbital cavity was performed with confirmation by histopathology of a poorly differentiated endophytic retinoblastoma with Bruch's membrane invasion. Follow-up sessions were then arranged as well as subsequent systemic chemotherapy cycles. CONCLUSION: Given the rare incidence of retinoblastoma in children older than 5 years old, it can be easily mistaken for other differential diagnoses and treated with filtration surgeries that could put the patient's life at risk. In this report, late-onset Rb diagnosis is highlighted as a differential diagnosis in children and adults with atypical uveitis, which required a multidisciplinary approach.

Burden and depression among informal caregivers of visually impaired patients in Mexico.

BACKGROUND: The needs of informal caregivers who provide care to family relatives with visual impairment are often neglected, resulting in burden and depression. OBJECTIVE: To determine the degree of burden and the prevalence of major depression experienced by caregivers, defined as non-paid family relatives, of legally blind individuals in a Mexican population. METHODS: Observational, single-center, cross-sectional study in adults providing care to their family relatives with visual impairment (visual acuity ≤ 20/200 in the best eye for at least 3 months). According to visual impairment degree, care provided included activities of daily living (ADL) and instrumental ADL. Burden of care was evaluated with the Zarit burden interview (ZBI)-22 and the prevalence of major depression was determined by the patient health questionnaire (PHQ)-9. RESULTS: 115 patients and 115 caregivers were included. Male caregivers had significantly higher ZBI-22 (28.7 ± 15.5 vs. 19.2 ± 12.6, p = 0.001) and PHQ-9 (10.0 ± 5.5 vs. 5.3 ± 5.1, p < 0.001) scores than females. Likewise, parent caregivers of adult children and the hours of daily care were significantly associated with higher burden and depression scores. A significant linear correlation between ZBI-22 and PHQ-9 scores in caregivers was also found (r = 0.649, p < 0.001). CONCLUSIONS: Male caregivers, parent caregivers of adult children, and caregivers providing greater hours of care were at higher risk of burden and depression. Upon diagnosis of visual impairment, adults providing care to visually impaired family relatives should be screened for burden and depression and referred to a mental health specialist when necessary. Tailored interventions targeting the caregivers' needs are required to reduce burden and depression.

Novel RB1 germline mutation in a healthy man.

BACKGROUND: Retinoblastoma (Rb) most frequently presents as a unilateral sporadic disease up to 40% of cases, however, arise from a monoallelic germline pathogenic variant. Only 10% of the germline mutations are inherited, and high penetrance is seen in up to 90% of these cases. As an effort to optimize counseling and screening, mutations are classified according to inheritance patterns. However, RB1 spectrum is highly heterogeneous, and information for unaffected carriers remains scarce. MATERIALS AND METHODS: The Mexican family of a 5-month-old patient diagnosed with Rb was studied. The family consisted of five individuals (father, mother, and three siblings). Genetic testing using a next-generation sequencing assay targeting RB1 with oligonucleotide baits designed to capture its exons and 20 bases flanking intronic sequences was performed in every family member. Clinical history and a complete ophthalmological examination (best-corrected visual acuity, slit-lamp biomicroscopy, macular optical coherence tomography, fundus autofluorescence, optical coherence tomography angiography, and electrophysiological studies) were performed in members testing positive to RB1 mutation. RESULTS: The father and her five-month-old daughter tested positive for a non-synonymous RB1 mutation c.459del (p.Lys154Serfs*21). The girl presented with bilateral retinoblastoma, successfully treated with cryotherapy and intravenous chemotherapy. The father had no relevant findings on imaging studies or ophthalmologic evaluation. CONCLUSIONS: This report describes a rare case of a novel low-penetrance RB1 germline mutation. Long-term follow-up of the father will include periodic evaluation of the eyes and orbits, and surveillance for systemic sarcoma and secondary malignancies. Implications for unaffected individuals need to be further studied.

The clinical and pathogenic spectrum of surgically-induced scleral necrosis: A review.

The onset of scleral necrosis after ocular surgery may have catastrophic ocular and systemic consequences. The two most frequent surgeries causing surgically-induced scleral necrosis (SISN) are pterygium excision and cataract extraction. Several pathogenic mechanisms are involved in surgically induced scleral necrosis. All of them are poorly understood. Ocular trauma increasing lytic action of collagenases with subsequent collagen degradation, vascular disruption leading to local ischemia, and immune complex deposition activating the complement system represents some of the events that lead to scleral necrosis. The complex cascade of events involving different pathogenic mechanisms and the patient's abnormal immune response frequently leads to delayed wound healing that predisposes the development of scleral necrosis. The management of SISN ranges from short-term systemic anti-inflammatory drugs to aggressive immunosuppressive therapy and surgical repair. Therefore, before performing any ocular surgery involving the sclera, a thorough ophthalmic and systemic evaluation must be done to identify high-risk patients that may develop SISN.

Diffuse infiltrative retinoblastoma with retinal detachment in "cinnamon-roll" configuration: a case report.

A 4-year-old girl presented with leukocoria, vision loss, and painless left eye redness. Posterior segment examination revealed a total retinal detachment and abnormal, tortuous retinal vessels in the left eye. No visible mass, vitreous seeding, or hemorrhage were observed. B-mode ultrasound showed a detached retina in a "cinnamon-roll" configuration. Due to poor visual prognosis and high clinical suspicion of malignancy, enucleation was performed. Further histopathological analysis confirmed the diagnosis of diffuse infiltrative retinoblastoma, with an atypical presentation.

Challenge of Retinoblastoma in Mexico in 2020: Perspectives and Solutions.

Early diagnosis and positive outcomes of retinoblastoma in childhood have been positively correlated with the economic wealth of high-income countries (HICs) worldwide. Adequate curability and survival rates, adherence to treatment, presence of poor prognostic initial clinical signs, and metastatic disease at diagnosis appear to have a less favorable picture in low-income countries (LICs). However, this is not always the case. An example is Argentina, where disease-free survival rates of retinoblastoma are notably higher than expected when taking into consideration its economic situation. Unfortunately, as in other Latin American LICs, retinoblastoma outcomes in Mexico are worrisome. Interestingly, the Human Development Index (HDI) in Mexico varies widely between its different geographical regions. While in some states, the HDI resembles those of high-income countries, and in others, the opposite is observed. A unifying picture of Mexico's developmental status, health resources, indicators, and other factors possibly influencing outcomes in retinoblastoma is currently unavailable. The present review explores the previously mentioned factors in Mexico and compares them to other countries. Additionally, it recommends solutions or enhancements where possible.