Adams-Oliver syndrome associated with refractory glaucoma.

Adams-Oliver syndrome (AOS) is a rare inherited disorder characterized by aplasia cutis congenita, cutis marmorata telangiectatica congenita, and terminal limb defects. Ocular associations have been rarely reported. We report a 6-month-old boy with AOS associated with refractory glaucoma, megalocornea, and anterior polar cataract. To our knowledge, this is the first case of glaucoma to be reported in association with AOS.

Glaucoma in Uveitic Eyes: Long-Term Clinical Course and Management Measures.

BACKGROUND: The management of glaucoma in uveitis is challenging. A meticulous combination of anti-glaucoma and anti-inflammatory agents is often needed to control the intraocular pressure (IOP) and preserve the visual status in an otherwise blinding disease. AIM: To study the clinical course and management of glaucoma in uveitic eyes. METHODS: A retrospective study analyzing the case records of patients over 12 years, referred for the management of uveitic glaucoma in the last two decades. RESULTS: The analysis of 582 uveitic glaucoma eyes of 389 patients was done, and the mean IOP at baseline was 25.89 (±13.1) mmHg. Non-granulomatous uveitis (102 eyes) was the most common diagnosis. Granulomatous uveitis was the most common diagnosis among the treatment failure eyes and in eyes requiring more than one surgical intervention for glaucoma. CONCLUSION: An appropriate and adequate combination of anti-inflammatory and IOP-lowering therapy will lead to better clinical outcomes.

Secondary Childhood glaucoma - a rare association in Seckel syndrome.

A case of 12-year-old male with Seckel syndrome, presented with unilateral glaucoma leading to advanced disc damage hence, visual deterioration. Seckel syndrome being a rare inherited disorder characterized by growth delay and unique facial features, had been infrequently reported for ophthalmic anifestation especially glaucoma. Though glaucoma is a rare association in Seckel syndrome, screening at an early stage could help in preventing vision loss.

A rare case of spontaneous expulsive suprachoroidal haemorrhage in a glaucomatous eye treated with topical alpha-adrenergic agonist.

Spontaneous expulsive suprachoroidal hemorrhage is a rare ocular condition, which usually occurs after sudden decompression of the eyewall. Most of the cases of expulsive hemorrhage reported had a predisposing glaucoma with the combination of corneal pathology. We are reporting a case of spontaneous expulsive suprachoroidal hemorrhage in a glaucoma patient probably due to perpetuated inflammatory reaction and frequent eye rubbing induced by allergic reaction to topical alpha adrenergic agonist in a compromised cornea.

Long-Term Surgical Outcomes of Primary Congenital Glaucoma in a South Indian Population.

PURPOSE: To evaluate the long-term surgical outcomes of children with primary congenital glaucoma (PCG) in a South Indian population. DESIGN: Retrospective cohort study. PARTICIPANTS: Children with PCG who underwent primary surgery from 1997 through 2000 at a tertiary eye center in India with minimum of 5 years of follow-up. METHODS: This retrospective cohort study included children with PCG who underwent trabeculotomy, trabeculectomy, or combined trabeculotomy and trabeculectomy (CTT) as primary surgery from 1997 through 2000 at a tertiary eye center in India with minimum of 5 years of follow-up. Survival analyses were performed to determine cumulative probability of complete and qualified success. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) control, glaucoma medication use, surgical success rates, and complications. RESULTS: The study included 50 eyes of 31 patients. Mean age at initial surgery was 5 months (range, 5 days-48 months) and 19 patients (61.3%) showed bilateral disease. Mean duration of follow-up was 10.9 ± 3.10 years (range, 6-18 years). Mean IOP was reduced from 28.58 ± 9.78 mmHg (range, 10-59 mmHg) before surgery to 17.13 ± 7.62 mmHg after surgery (range, 5-42 mmHg; P < 0.001) at final follow-up. Survival analysis showed that the probability of surgical success with CTT was 77.8% at 1 year, 66.2% at 2 years, 53.0% at 5 years, and 16.6% at 15 years. Visual acuity at last available follow-up correlated with surgical success (P = 0.042). CONCLUSIONS: Surgical success after long-term follow-up of children with PCG is low. The probability of surgical success declines over time. Children with PCG require life-long follow-up and management, even after initial surgical success, to prevent visual impairment and blindness.

Understanding Barriers to Glaucoma Treatment Adherence among Participants in South India.

Purpose: Data on glaucoma treatment barriers in South India is limited; improved knowledge of barriers could advance disease self-management. We aimed to understand glaucoma treatment barriers in South India.Methods: Glaucoma patients ≥18 taking ≥1 medication at the Aravind Eye Hospital were screened with a validated medication adherence tool. Patients who self-reported poor adherence and/or were >3 months late for follow-up completed semi-structured interviews on treatment barriers. Interviews were audio-recorded, transcribed, translated and back-translated to ensure accuracy. Researchers used grounded theory to code the transcripts and identify themes using NVivo 11.0. Demographic and clinical characteristics were abstracted from the medical record.Results: 70/167 (42%) had poor self-reported adherence to drops. The 45 interviewed were 62 ± 12 years and took 1.6 ± 0.7 drops. Forty-two (93%) were non-adherent to medication and 21 (47%) were late for follow-up. Top barriers to medication adherence were difficulty obtaining drops (20, 44%), being busy (18, 40%), and the expense (17, 38%). Top barriers to appointment follow-up were distance to the hospital (21, 47%), expense (20, 44%), and no escort (15, 33%). Other important barriers included mistrust in the health system, poor knowledge of glaucoma and family needs.Conclusions: Previously, 6% of glaucoma patients in South India self-reported poor medication adherence; the 42% identified in this study is in line with glaucoma medication adherence rates globally. Complex factors caused high rates of non-adherence. Societal-level interventions that address systemic barriers and counselling that supports patients' and families' motivation for behaviour change should be implemented.

A Rare Case Report of Frank Ter Haar Syndrome in a Sibling Pair Presenting With Congenital Glaucoma.

Frank Ter Haar syndrome (FTHS) is a rare autosomal recessive disorder with characteristic skeletal, cardiac, ocular, and craniofacial abnormalities. We report a sibling pair presenting with clinical features typical of FTHS, born to consanguineous parents, with a novel mutation in the SH3PXD2B gene on chromosome 5q35.1 that results in premature truncation of the protein encoded. The children presented with brachycephaly, multiple joint contractures, cardiac valvular defects, bilateral megalocornea, and congenital glaucoma. Trabeculotomy combined with trabeculectomy was performed in both siblings to control intraocular pressure. The characteristic clinical features with the underlying genetic defects confirmed the diagnosis of FTHS. Early diagnosis and treatment of congenital glaucoma preserved vision in the children.

Quantification of RAPD by an automated pupillometer in asymmetric glaucoma and its correlation with manual pupillary assessment.

PURPOSE: The relative afferent pupillary defect (RAPD) is an important sign of asymmetrical retinal ganglion cell damage. The purpose of this study was to quantify RAPD by a pupillometer (RAPiDo, Neuroptics) and assess its correlation with asymmetric glaucoma and manual pupillary assessment. METHODS: A total of 173 subjects were enrolled in the study and categorized into glaucoma, n = 130, and control, n = 43. Subjects were all recruited in the Glaucoma Clinic of the Aravind Eye Hospital in Madurai during their follow-up. They were 18 years and older, with best corrected visual acuity of 6/36 or better. Exclusion criteria included all retinal pathologies, optic atrophies, ocular injuries, severe uveitis, cloudy corneas, dense cataracts, or use of mydriatics or miotic drugs. RAPD was assessed in all subjects using an automated pupillometer and the results were compared with the swinging flash light test conducted on the same subjects by an experienced ophthalmologist. We looked at the correlation between RAPD and the intereye difference in cup-to-disc ratio (CDR), mean deviation (MD) of visual field testing, and retinal nerve fiber layer (RNFL) thickness. Sensitivity and specificity were assessed by area under the receiver operator characteristic (AUROC) analysis. RESULTS: Glaucoma patients had significant RAPD (0.55 ± 0.05 log units) when compared with the controls (0.25 ± 0.05 log units), P < 0.001. Significant intereye differences in CDR, MD, and RNFL between glaucoma and control (P < 0.001) were seen. There was a good correlation between the magnitude and sign of RAPD and these intereye differences in CDR (r = 0.52, P < 0.001), MD (r = 0.44, P < 0.001) and RNFL thickness (r = 0.59, P < 0.001). When compared with the experienced ophthalmologist, AUROC was 0.94, with 89% sensitivity and 91.7% specificity. CONCLUSION: The good correlation between the magnitude of RAPD, as measured by the automated pupillometer, and intereye differences in MD, CDR, and RNFL thickness in glaucomatous, and the good sensitivity and specificity when compared with the experienced ophthalmologist, suggest that pupillometry may be useful as a screening tool to assess asymmetric glaucoma.

Glaucoma-Associated Visual Task Performance and Vision-Related Quality of Life in South India.

Objective/Purpose: Performance-based measures may provide an objective assessment of how glaucoma affects daily functioning. We sought to validate a clinically-applicable performance-based measure of visual ability for patients with glaucoma in south India and to describe its relationship to clinical and patient-reported outcomes. Design: Cross-sectional validation study. Subjects/Participants/Controls: 145 participants with glaucoma were recruited at Aravind Eye Hospital. Methods/Intervention/Testing: We modified the compressed assessment of activities related to vision (CAARV), a performance-based measure validated in the U.S., to be culturally relevant in south India. Participants underwent a series of tests, including the Indian CAARV (I-CAARV), Indian Visual Functioning Questionnaire (IND-VFQ), Spaeth/Richman Contrast Sensitivity (SPARCS) test, standard automated perimetry, and visual acuity (VA). Factor analysis and Rasch modeling were used to validate the I-CAARV. Correlations between the I-CAARV and other outcomes were evaluated. Main Outcome Measure: Psychometric properties of the I-CAARV for individuals with glaucoma in south India. Results: The study included 142 participants (51.7% female, mean age 56.4 years). Average presenting visual acuity and visual field mean deviation (MD) in the better-seeing eye were 0.26 logMAR and -6.57 dB, respectively. The four tasks of the I-CAARV were found to measure a single underlying construct. Rasch analysis of the I-CAARV revealed that the outcome measure had moderate reliability, good construct and content validity, and fair measurement precision. Tasks were well-targeted to the study sample. Rasch-calibrated scores on the I-CAARV were significantly correlated with Rasch-calibrated IND-VFQ scores (r=-0.54) and with visual field MD, presenting VA, best-corrected VA, and SPARCS contrast sensitivity in both the better-seeing eye (r=0.60, -0.51, -0.53, 0.76, respectively) and worse-seeing eye (r=0.48, -0.61, -0.46, 0.69, respectively). Conclusions: The I-CAARV is a valid performance-based measure of vision-dependent functioning in glaucoma in south India. This study also found that I-CAARV task performance was strongly correlated with contrast sensitivity and suggests that performance-based and patient-reported outcomes are related but distinct measures of the impact of glaucoma on functioning and vision-related quality of life. Future studies are needed to determine the sensitivity of the I-CAARV to detect changes due to disease progression that are relevant to functioning and vision-related quality of life.

Caregiver Burden in Primary Congenital Glaucoma.

PURPOSE: To evaluate the demographic, clinical, and socioeconomic factors associated with variation in the quality of life (QOL) in caregivers of children with primary congenital glaucoma (PCG) in south India. DESIGN: Cross-sectional survey. METHODS: Caregivers of children younger than 18 with diagnosed PCG were prospectively enrolled at Aravind Eye Hospital in Madurai and Coimbatore, India. Participants completed 2 questionnaires, the PHQ-9 (9-item Patient Health Questionnaire) and the CarCGQoL (Caregivers Congenital Glaucoma QOL Questionnaire). Clinical, demographic, and socioeconomic data were obtained for each child-caregiver dyad. Rasch-calibrated scores were calculated for patient-reported outcome measures. Spearman correlation and linear regression were used to analyze data to determine associations with caregiver QOL. RESULTS: There were 70 caregivers (mean age 32.1, 77.1% female) of 70 children with PCG (mean age 7.7, 37.1% female) included in the study. In univariate and multivariable analyses, child's age (ß = -0.04; 95% confidence interval, -0.08 to -0.01) and duration of disease (ß = - 0.03; 95% confidence interval, -0.07 to -0.01) were the only factors associated with CarCGQoL. Survey items related to anger, self-confidence, irritability, appetite, and interest in leisure activities had the lowest scores. There was a negative correlation between CarCGQoL and PHQ-9 scores (r = -0.66, P < .01), indicating that worse caregiver QOL was significantly correlated with more depressive symptoms. CONCLUSION: This study identified traits associated with QOL decline, as well as the QOL issues most likely to affect caregivers of children with PCG in south India. Findings from this study may be important for designing interventions to improve caregivers' QOL, thereby maximizing their ability to care for children with PCG.

A rare case of overlapping Sturge-Weber syndrome and Klippel-Trenaunay syndrome associated with bilateral refractory childhood glaucoma.

A 6-year-old girl presented with blurred vision and was found to have elevated intraocular pressure (IOP) and glaucomatous optic disc damage in both eyes. She also displayed capillary malformations on the face (port-wine stain), upper back and all four limbs, angiomatosis in the brain and had hypertrophy of the left upper and lower limbs typical of overlapping Sturge-Weber syndrome and Klippel-Trenaunay syndromes. She was initially managed with IOP lowering topical medications but required trabeculectomy in the right eye followed by Ahmed valve implantation in both eyes. Despite multiple measures over a 7-year period, her IOP still remained uncontrolled with gradual progression of the glaucomatous damage. This case exhibits a very rare occurrence of overlapping syndromes reported only a handful of times in literature. Most cases with Sturge-Weber syndrome have ipsilateral glaucoma affecting the eye on the same side as the port-wine stain. This case presented with bilateral refractory childhood glaucomas, which is exceedingly rare.

Identification and characterization of variants and a novel 4 bp deletion in the regulatory region of SIX6, a risk factor for primary open-angle glaucoma.

BACKGROUND: Primary open-angle glaucoma (POAG) is a complex disease of multigenic inheritance and the most common subtype of glaucoma. SIX6 encodes a transcription factor involved in retina, optic nerve, and pituitary development. Previous studies showed a genetic association between the SIX6 locus and POAG, identifying risk alleles. Whether these alleles are present also in the south Indian population is unclear. METHODS: To address this question, the SIX6 gene and an already characterized and highly conserved SIX6 enhancer (Ch14:60974427-60974430) were sequenced in two south Indian cohorts, respectively, composed of 65/65 and 200/200 POAG cases/age-matched controls. We next used Taqman-based allelic discrimination assay to genotype a common variant (rs33912345: c.421A>C) and the rs1048372 SNP in two cohorts, respectively, composed of 557/387 and 590/448 POAG cases/age-matched controls. An additional cohort of 153 POAG cases was subsequently recruited to assess the association of the rs33912345:c.421A>C and rs10483727 variants with more prominent changes in two POAG diagnostic parameters: retinal nerve fiber layer thickness and vertical cup/disc ratio, using spectral domain optical coherence tomography. The activity of the newly identified enhancer variants was assessed by transgenesis in zebrafish and luciferase assays. RESULTS: We identified two known rare and two common variants in the SIX6 locus and a novel 4 bp deletion in the analyzed enhancer. Contrary to previous studies, we could not establish a significant association between the rs10483727 and rs33912345:c.421A>C variants and PAOG in the south Indian ethnicity but patients carrying the corresponding C or T risk alleles exhibited a dose-dependent reduction of the thickness of the retinal nerve fiber layer and a significant increase in the vertical cup/disc ratio. Transgenesis in zebrafish and luciferase assays demonstrated that the newly identified 4 bp deletion significantly reduced reporter expression in cells of the retinal ganglion and amacrine layers, where human SIX6 is expressed. CONCLUSION: Altogether, our data further support the implication of SIX6 variants as POAG risk factors and implicates SIX6 haploinsufficiency in POAG pathogenesis.

Effectiveness of Glaucoma Counseling on Rates of Follow-up and Glaucoma Knowledge in a South Indian Population.

PURPOSE: To evaluate the impact of traditional counseling and patient-centered counseling, either alone or with recorded audio counseling reinforcement, on glaucoma knowledge and clinical follow-up. DESIGN: Prospective randomized controlled trial. METHODS: Newly diagnosed adult glaucoma patients were randomized to 1 of 3 categories of glaucoma counseling: traditional counseling, patient-centered counseling, or patient-centered counseling with audio counseling reinforcement. Demographic and clinical information from each subject was ascertained, and all subjects completed the Glaucoma Knowledge Assessment before and after counseling sessions at the time of diagnosis and at 1-month follow-up. Patients were instructed to return to clinic for routine follow-up at 1, 3, 6, 9, and 12 months after enrollment. A multivariate logistic regression model was used to determine factors associated with appropriate clinical follow-up. RESULTS: Overall, only 13.5% of subjects had appropriate clinical follow-up at 1 year, defined as attending at least 3 follow-up visits during that interval, and there was no significant difference between counseling groups. The mean glaucoma knowledge assessment score (GKAS) improved by 77.6% with the initial counseling intervention (P < .0001), decreased by 17.4% within a 1-month period following initial counseling, and improved by 22.8% (P < .001) after the second counseling intervention. Monthly household income over 2500 rupees, GKAS greater than 5 after initial counseling, and undergoing any ocular surgical procedure were all independent predictors of appropriate follow-up. CONCLUSION: While all 3 counseling methods resulted in transient improvement of patient knowledge regarding glaucomatous disease, follow-up rates were poor for all groups. Poor retention of glaucoma knowledge may impact the likelihood of patient follow-up, and reinforcement with repeated counseling may be beneficial with regard to both disease knowledge and follow-up.

Comparison of a travoprost BAK-free formulation preserved with polyquaternium-1 with BAK-preserved travoprost in ocular hypertension or open-angle glaucoma.

PURPOSE: To demonstrate that the intraocular pressure (IOP)-lowering effect of travoprost 0.004% preserved with polyquaternium-1 (travoprost benzalkonium chloride [BAK]-free) is non-inferior to that of travoprost 0.004% preserved with benzalkonium chloride (travoprost BAK) in patients with ocular hypertension or open-angle glaucoma. METHODS: A total of 371 patients randomly received travoprost BAK-free (n=185) or travoprost BAK (n=186) dosed once daily in the evening for 3 months. Patients were evaluated at 9 am, 11 AM, and 4 PM at baseline, weeks 2 and 6, and month 3. Intraocular pressure was also evaluated 36 and 60 hours after the month 3 visit. RESULTS: Travoprost BAK-free is non-inferior to travoprost BAK. The 95% upper confidence limits for the difference in mean IOP at month 3 (primary efficacy) were 0.5 mmHg, 0.6 mmHg, and 0.5 mmHg, at 9 AM, 11 AM, and 4 PM, respectively. Mean IOP reductions from baseline ranged from 7.6 to 8.7 mmHg in the travoprost BAK-free group and from 7.7 to 9.2 mmHg in the travoprost BAK group. At 36 and 60 hours after the last dose, mean IOP remained 6.8 mmHg and 5.7 mmHg below baseline in the travoprost BAK-free group, vs 7.3 mmHg and 6.0 mmHg in the travoprost BAK group, respectively. The safety profile of travoprost BAK-free was similar to that of travoprost BAK. CONCLUSIONS: Travoprost BAK-free safely and effectively lowers IOP in eyes with open-angle glaucoma or ocular hypertension. This BAK-free formulation has comparable safety, efficacy, and duration of IOP-lowering effect to travoprost preserved with BAK. Travoprost BAK-free is an effective option for IOP reduction while avoiding BAK exposure.