Sociodemographic disparities in ophthalmological clinical trials.

INTRODUCTION: In ophthalmology, clinical trials (CTs) guide the treatment of diseases such as diabetic retinopathy, myopia, age-related macular degeneration, glaucoma and keratoconus with distinct presentations, pathological characteristics and responses to treatment in minority populations.Reporting gender and race and ethnicity in healthcare studies is currently recommended by National Institutes of Health (NIH) and Food and Drug Administration (FDA) guidelines to ensure representativeness and generalisability; however, CT results that include this information have been limited in the past 30 years.The objective of this review is to analyse the sociodemographic disparities in ophthalmological phases III and IV CT based on publicly available data. METHODS: This study included phases III and IV complete ophthalmological CT available from clinicaltrials.org, and describes the country distribution, race and ethnicity description and gender, and funding characteristics. RESULTS: After a screening process, we included 654 CTs, with findings that corroborate the previous CT reviews' findings that most ophthalmological participants are white and from high-income countries. A description of race and ethnicity is reported in 37.1% of studies but less frequently included within the most studied ophthalmological specialty area (cornea, retina, glaucoma and cataracts). The incidence of race and ethnicity reporting has improved during the past 7 years. DISCUSSION: Although NIH and FDA promote guidelines to improve generalisability in healthcare studies, the inclusion of race and ethnicity in publications and diverse participants in ophthalmological CT is still limited. Actions from the research community and related stakeholders are necessary to increase representativeness and guarantee generalisability in ophthalmological research results to optimise care and reduce related healthcare disparities.

Isolated aniridia caused by a novel PAX6 heterozygous deletion mediated by multi-exon complex rearrangement.

PURPOSE: Mutations in PAX6 gene (chromosome 11p13) encoding a transcriptional regulator involved in oculogenesis mostly present with aniridia. Aniridia is not uncommon in the Philippines but only limited information is available as yet. The purpose of this study was to present a novel, deletion mediated by complex rearrangement in PAX6 gene causing an isolated aniridia in a Filipino girl. PATIENTS AND METHODS: The patient is an 8-year-old girl who came in due to leukocoria with associated nystagmus and esotropia. She presented with subnormal vision, nystagmus, aniridia, and cataractous lenses in both eyes. The family history reveals presence of the aniridia and cataract with the mother and a sibling. The patient underwent lens extraction without intraocular lens implantation bilaterally, where patient subsequently underwent intraocular lens implantation on her left eye. Systemic workup was performed including whole abdomen, renal ultrasound, blood chemistry, and urinalysis. Targeted cataract panel with WT1 and PAX6 genes revealed a novel, heterozygous PAX6-inherited mutation from the mother. This variant is a complex rearrangement in PAX6 involving partial deletions of exons 3-5, including the initiator codon. Deletions of PAX6 are part of a contiguous gene deletion syndrome - Wilms tumor, aniridia, genitourinary anomalies, and intellectual disability syndrome - and therefore evaluation of the WT1 gene was necessary to rule out this life-threatening syndrome. CONCLUSION: This rare, complex rearrangement of multiple exons and deletions in PAX6 causing an isolated aniridia phenotype is probably the first reported case. The patient was managed by a multidisciplinary team and the guardians were counseled regarding the prognosis and complications.

Large bilateral medial rectus recession versus three-to-four horizontal muscle surgery for large-angle esodeviations.

PURPOSE: The best surgical approach to correcting large angle esodeviations is still debated. Options for correcting large esodeviations include recessing both medial rectus (BMR) muscles more than 5.5 mm or performing surgery on three or four horizontal rectus muscles. There remains no consensus on which surgery has better survival outcomes. In this research, we are interested in determining the survival rates and long-term outcomes of both surgeries locally in the Philippines. RESULTS: A total of 74 medical records were retrospectively reviewed. The mean age at onset of deviation was 2 ± 2.9 years old, and the mean age at surgery was 14 ± 12.5 years, with a mean of 12 ± 12.1 years from onset to surgery. The mean follow-up period was 9.9 months (range 6-24) . The mean preoperative deviation at near was 59.3 ± 13.6 PD (range: 35-95) while at distance was 58.5 ± 13.6 PD (range 10-95). The most common type of esotropia (ET) was infantile ET (45%), followed by basic ET. Majority of the esodeviations did not have associated vertical strabismus (67.6%, n = 50). Overall success rate was 48.1% for BMR recessions and 54.5% for 3-4 muscles surgery. Survival analysis revealed the decreasing trends of survival but plateauing of outcomes after 6 months. CONCLUSION: We reported the outcomes for both surgeries. Neither had shown superiority over the other. After a mean follow up of 9.9 months, the overall success was relatively good: 50% were successful, 39.2% overall recurrence and 13.8% overcorrections. Survival plots showed a plateauing of results after 6 months.

Evaluation of a Hirschberg Test-Based Application for Measuring Ocular Alignment and Detecting Strabismus.

Purpose: Photographic Hirschberg test applications are practical options for screening in areas where a specialist is not available. A semi-automated Hirschberg test-based application was developed and evaluated on its ability to detect and measure strabismus at distance and near fixation.Methods: This is a prospective cross-sectional inter-rater agreement study conducted at a tertiary hospital. Study A evaluated the ability of the application to determine the presence or absence of strabismus in subjects of unknown strabismus status (n = 28). Study B evaluated the ability of the application to measure the deviation of strabismic subjects (n = 8). All subjects underwent alternate prism cover test (APCT) at distance and near fixation. Facial photographs at distance and near fixation were taken. Each photograph underwent automated face and eye detection, manual limbus and corneal reflex identification, and strabismus detection and measurement.Results: The application obtained a matching rate of 95.14% for the face and eyes. The application yielded a sensitivity of 92.86% for horizontal strabismus at distance and near fixation, however, with low specificity values (7.692%, 14.81%, and 8%). The Bland-Altman plots derived from Study B showed bias values of application measurements between 3.625Δ and 6.125Δ with wide intervals of the limits of agreement. Repeatability of the measurements yielded bias values of -0.625Δ and 2.5Δ for horizontal and vertical strabismus at distance and 4.375Δ and 1.25Δ at near fixation, respectively.Conclusion: This semi-automated Hirschberg test-based application can effectively determine the face and eye location and shows potential as a screening tool for horizontal strabismus.

Novel compound heterozygous pathogenic BBS5 variants in Filipino siblings with Bardet-Biedl syndrome (BBS).

PURPOSE: Bardet-Biedl syndrome (BBS) is rare in the Philippines and only limited information on the prevalent subtypes is available as yet. The purpose of this study is to present the clinical characteristics of two Filipino siblings presenting with mutations in BBS5. PATIENTS AND METHODS: The Filipino female siblings, aged 11 and 14 years underwent comprehensive ophthalmologic evaluation. Fundus photography, macular optical coherence tomography (OCT) and electroretinography (ERG) were also obtained. Systemic workup was performed including radiographic imaging of limb defects, renal ultrasound, blood chemistry, and transvaginal ultrasound. Targeted Bardet-Biedl sequence analysis and deletion/duplication analysis were performed to determine potential pathogenic mutations. RESULTS: Both children had poor visual acuity with a myopic refraction. There was a pigmentary retinopathy with retinal pigment epithelium changes and attenuation of vessels without waxy disc pallor. Generalized macular thinning and undetectable ERG responses were recorded. Physical examination revealed obesity, facial anomalies, brachydactyly, postaxial polydactyly, and clinodactyly of fifth digits. Both patients displayed cognitive developmental delay and hypogonadism. Molecular analysis revealed novel compound heterozygous mutations in BBS5 with c.143-1 G > A (splice acceptor) and c.925_931del (p.Gln309ilefs*14), each inherited from one asymptomatic parent. CONCLUSION: These are probably the first reported BBS5 mutations causing Bardet-Biedl syndrome in the Philippines. Patients were managed by a multi-disciplinary team and the parents were counseled regarding the prognosis and additional complications associated with the syndrome.