Circular functional analysis of OCT data for precise identification of structural phenotypes in the eye.

Progressive optic neuropathies such as glaucoma are major causes of blindness globally. Multiple sources of subjectivity and analytical challenges are often encountered by clinicians in the process of early diagnosis and clinical management of these diseases. In glaucoma, the structural damage is often characterized by neuroretinal rim (NRR) thinning of the optic nerve head, and other clinical parameters. Baseline structural heterogeneity in the eyes can play a key role in the progression of optic neuropathies, and present challenges to clinical decision-making. We generated a dataset of Optical Coherence Tomography (OCT) based high-resolution circular measurements on NRR phenotypes, along with other clinical covariates, of 3973 healthy eyes as part of an established clinical cohort of Asian Indian participants. We introduced CIFU, a new computational pipeline for CIrcular FUnctional data modeling and analysis. We demonstrated CIFU by unsupervised circular functional clustering of the OCT NRR data, followed by meta-clustering to characterize the clusters using clinical covariates, and presented a circular visualization of the results. Upon stratification by age, we identified a healthy NRR phenotype cluster in the age group 40-49 years with predictive potential for glaucoma. Our dataset also addresses the disparity of representation of this particular population in normative OCT databases.

LVPEI Glaucoma Epidemiology and Molecular Genetic Study: teleophthalmology screening for angle-closure disease in an underserved region.

OBJECTIVES: To assess the ability of teleophthalmoscopic grading of peripheral anterior chamber depth (PACD) using the van Herick (vH) technique in detecting gonioscopically occludable angle; and to determine whether combining results from vH grading and ocular biometry can improve the accuracy to diagnose gonioscopically occludable angle METHODS: This cross-sectional study was an offshoot of a rural population-based study, Glaucoma Epidemiology and Molecular Genetic Study (GLEAMS). A masked urban ophthalmologist graded digital slit lamp photographs of PACD by vH technique. Sussman four-mirror lens was used to perform dark room indentation gonioscopy. Cutoff values of the tests were, vH technique: grade ≤ 2, central anterior chamber depth (ACD), as well as axial length: ≤ 25th percentile and lens thickness ≥ 75th percentile value of the study population. RESULTS: We studied 1965 eyes of 1029 adult participants. The vH grade was ≤2 in 188 (9.5%) eyes. The angle was occludable by gonioscopy in 101 (5.1%) eyes. The performance of the vH test to rule out gonioscopically occludable angle was good [negative predictive value (NPV): 97.3%], despite low sensitivity (52.5%), while its efficacy to rule in the condition was low [positive predictive value (PPV): 28.2%] despite high specificity (92.8%). However, test combination strategy increased the PPV nearly twofold (53.8%). The calculated PPV at 10% prevalence of gonioscopically occludable angle was even higher (70.5%). CONCLUSIONS: Van Herick technique can be incorporated into a teleophthalmology program by means of slit lamp photographs of PACD. Combined vH grading and ocular biometry improved the predictability of a gonioscopically occludable angle.

Prevalence of Primary Glaucoma as Diagnosed by Study Optometrists of L. V. Prasad eye Institute - Glaucoma Epidemiology and Molecular Genetics Study.

PURPOSE: To report the prevalence of primary glaucoma as identified by study optometrists of the L. V. Prasad Eye Institute - Glaucoma Epidemiology and Molecular Genetics Study (LVPEI-GLEAMS). METHODS: Two study optometrists and a total number of 3833 individuals participated in the LVPEI-GLEAMS. All subjects underwent a complete medical history and comprehensive eye examination including slit lamp photography, imaging of anterior and posterior segment, frequency doubling technology and standard automated perimetry including gonioscopy with a Sussman 4 mirror goniolens, post dilated evaluation of the optic disc and fundus was done with a 90 D lens by the study optometrist. A diagnosis of primary open angle glaucoma (POAG), primary angle closure suspect (PACS), primary angle closure (PAC), primary angle closure glaucoma (PACG), normal tension glaucoma (NTG), glaucoma/disc suspect or no glaucoma was made based on the clinical examination. RESULTS: Estimated prevalence of OAG (POAG and NTG) was 1.07% (0.74-1.39), PACS 2.03% (1.58-2.48), PAC 1.77% (1.35-2.19), PACG 0.21% (0.06-0.35) as identified by the study optometrists on site. CONCLUSIONS: Prevalence of all the categories of primary glaucoma, as reported by the study optometrists of LVPEI-GLEAMS was comparable to previous findings of other regions in South India.

Scanning the macula for detecting glaucoma.

BACKGROUND: With the advent of spectral domain optical coherence tomography (SDOCT), there has been a renewed interest in macular region for detection of glaucoma. However, most macular SDOCT parameters currently are thickness parameters which evaluate thinning of the macular layers but do not quantify the extent of area over which the thinning has occurred. We therefore calculated a new macular parameter, "ganglion cell complex surface abnormality ratio (GCC SAR)" that represented the surface area over which the macular thickness was decreased. PURPOSE: To evaluate the ability of SAR in detecting perimetric and preperimetric glaucoma. DESIGN: Retrospective image analysis. MATERIALS AND METHODS: 68 eyes with perimetric glaucoma, 62 eyes with preperimetric glaucoma and 165 control eyes underwent GCC imaging with SDOCT. SAR was calculated as the ratio of the abnormal to total area on the GCC significance map. STATISTICAL ANALYSIS: Diagnostic ability of SAR in glaucoma was compared against that of the standard parameters generated by the SDOCT software using area under receiver operating characteristic curves (AUC) and sensitivities at fixed specificities. RESULTS: AUC of SAR (0.91) was statistically significantly better than that of GCC average thickness (0.86, P = 0.001) and GCC global loss volume (GLV; 0.88, P = 0.01) in differentiating perimetric glaucoma from control eyes. In differentiating preperimetric glaucoma from control eyes, AUC of SAR (0.72) was comparable to that of GCC average thickness (0.70, P > 0.05) and GLV (0.72, P > 0.05). Sensitivities at specificities of 80% and 95% of SAR were comparable (P > 0.05 for all comparisons) to that of GCC average thickness and GLV in diagnosing perimetric and preperimetric glaucoma. CONCLUSION: GCC SAR had a better ability to diagnose perimetric glaucoma compared to the SDOCT software provided global GCC parameters. However, in diagnosing preperimetric glaucoma, the ability of SAR was similar to that of software provided global GCC parameters.

Glaucoma in microspherophakia: presenting features and treatment outcomes.

PURPOSE: To report the clinical features, management, and treatment outcomes of glaucoma in microspherophakia. METHODS: Medical records of 159 eyes of 80 subjects with microspherophakia were reviewed. The clinical features at presentation, presence of glaucoma, methods of treatment, and their outcomes were noted. Glaucoma was diagnosed based on intraocular pressure (IOP)≥22 mm Hg on 2 different occasions and/or glaucomatous optic disc damage. Angle closure was defined as occludable angles >270 degrees with or without presence of peripheral anterior synechiae. RESULTS: Glaucoma was diagnosed in 81 eyes (51%). The mean age of subjects was 20±13 years, mean refractive error was -13.5±5.5, the mean IOP was 27.7±11.1 mm Hg. IOP≥22 mm Hg was present in 84% of eyes, disc damage in 59% of the eyes, 75% eyes had angle closure, and 25% had open angle on gonioscopy. Subluxation of crystalline lens was seen in 53 eyes and 14 eyes had dislocation of the lens; systemic associations were present in 21 subjects (3 Marfan syndrome, 18 Weill-Marchesani syndrome). Nine eyes out of 51 and 2 out of 16 eyes responded to medical treatment and laser iridotomy, respectively. Of the 48 eyes that required surgical intervention, 24 eyes underwent trabeculectomy. Complete success probability of trabeculectomy was 86% [95% confidence interval (CI), 63%-95%] at 6 months, 77% (95% CI, 53%-90%) at 1 year, which was maintained till 7 years, and reduced to 61% (95% CI, 26%-84%) at 8 years. Nearly 20% of eyes at presentation and 30% of the eyes at last follow-up were blind due to glaucoma. CONCLUSIONS: More than half of the eyes with microspherophakia in this series presented with glaucoma; angle closure was the predominant form of glaucoma. Blindness due to glaucoma in microspherophakia was 20% to 30%.

LV Prasad Eye Institute Glaucoma Epidemiology and Molecular Genetic Study (LVPEI- GLEAMS). Report 1: study design and research methodology.

PURPOSE: In the developing world, more than 90% of glaucoma is undetected due to the lack of appropriate screening methods. The LV Prasad Eye Institute Glaucoma Epidemiology and Molecular Genetic Study (LVPEI-GLEAMS) is a population-based study which aims to estimate the prevalence of, along with clinical, systemic and genetic risk factors for glaucoma in a rural population sampled from the state of Andhra Pradesh, India. The study aims to develop community screening strategies to diagnose glaucoma. This article describes the methodology adopted in LVPEI-GLEAMS. METHODS: A sample of 3833 participants aged 40 years and older has been estimated to be enrolled using a compact segment sampling method with probability proportionate to size. Each participant will undergo a complete medical history and comprehensive eye examination including slit lamp photography, imaging of anterior and posterior segment, frequency doubling technology and standard automated perimetry. Additionally, glycosylated hemoglobin will be measured and a genetic profile based on candidate gene analysis will be undertaken. Clinical, biochemical and genetic data will be stored in a computerized database and analyzed. The novelty of this study lies in the fact that it is conducted at a vision center (primary eye care center serving a population of 50,000) by a vision technician (high school educated rural youth trained in basic ophthalmic techniques for a year). CONCLUSION: Information from the diagnostic techniques of the study will be used to develop effective community-level screening strategies, and insights from risk factors associated with glaucoma will help develop appropriate detection and management strategies.

Relationship between intraocular pressure and rate of visual field progression in treated glaucoma.

PURPOSE: To evaluate the relationship between intraocular pressure (IOP) and the rate of visual field (VF) progression in treated glaucoma. METHODS: In a clinic-based, retrospective study, data of consecutive primary open-angle and angle-closure glaucoma patients with ≥ 5 VFs between 1989 and 2008 were analyzed. The Guided Progression Analysis software, which provides the rate of change of Visual Field Index per year, was used to assess the rate of progression (ROP). IOP measurements during the VF examination visits were extracted, and mean, peak, and fluctuation (SD) of IOP during the follow-up were calculated. Relationships between IOP parameters and ROP were analyzed using regression models. Other risk factors evaluated were age, sex, type of glaucoma, presence of hypertension and diabetes, severity of VF loss at presentation, glaucoma surgery during follow-up, number of antiglaucoma medications, and follow-up duration. RESULTS: During the study period, 296 eyes of 213 glaucoma patients had undergone ≥ 5 VFs. IOP fluctuation was the only IOP parameter significantly associated with ROP (ß=-0.37, P=0.02). Evaluated in a multivariate model with other risk factors, the severity of VF damage at presentation (ß=0.08, P=0.002) and IOP fluctuation (ß=-0.35, P=0.02) remained significantly associated with ROP. Greater IOP fluctuation was seen in eyes undergoing glaucoma surgery and eyes requiring more antiglaucoma medications during follow-up. CONCLUSIONS: Long-term IOP fluctuation was the most important IOP parameter associated with increased ROP of glaucomatous VF loss. This association is likely due to the confounding effect of enhanced therapy in eyes suspected to be progressing.

Effect of cataract extraction on Visual Field Index in glaucoma.

PURPOSE: : To determine the effect of cataract on the Visual Field Index (VFI) in glaucoma patients. METHODS: : Reliable visual fields (VFs) of 53 patients (53 eyes) with primary glaucoma who underwent phacoemulsification either alone or combined with trabeculectomy were analyzed before and after surgery. All patients had VFs within a period of 15 months before and after surgery. VFI, mean deviation (MD), and pattern standard deviation (PSD) before surgery were compared with those after surgery. RESULTS: : Median (25th and 75th percentiles) MD after cataract surgery [-10.52 dB (range, -19.25 to -4.86 dB)] was significantly better (P=0.003) than that before surgery [-11.74 dB (range, -20.61 to -7.15 dB)]. Median PSD after surgery [4.76 dB (range, 2.48 to 9.83)] was worse (P=0.01) than that before surgery [3.50 dB (range, 1.93 to 8.20 dB)] when eyes with MD better than -20 dB were considered (41 eyes). VFI after surgery [80% (range, 44% to 94%)] was similar (P=0.92) to that before surgery [77% (range, 37% to 92%)]. MD improved while VFI remained unchanged in both nuclear sclerotic (n=41) and posterior subcapsular cataracts (n=12). CONCLUSIONS: : MD and PSD were significantly affected, whereas VFI was not affected by cataract. VFI may be a more robust measure of VF damage than MD or PSD in glaucomatous eyes with coexisting cataracts.

Effect of optic disc size and disease severity on the diagnostic capability of glaucoma imaging technologies in an Indian population.

PURPOSE: To evaluate the influence of optic disc size and disease severity on the diagnostic validity of optical coherence tomography (Stratus OCT), scanning laser polarimetry [GDx variable corneal compensator (VCC)], and confocal scanning laser ophthalmoscopy [Heidelberg retina tomograph II (HRT II)] in Indian eyes with glaucoma. METHODS: Ninety-five normal and 125 glaucoma patients underwent imaging with Stratus OCT, GDx VCC, and HRT II. One eye of each person was randomly selected for analysis. Using disc area determined on HRT II, discs were classified as small (<2 mm), moderate (2 to 3 mm), and large (>3 mm). The parameter with the best sensitivity for each device, at a fixed specificity, was compared for different disc sizes. Logistic marginal regression was used to study the effect of disc size and disease severity (mean deviation on standard automated perimetry) on the diagnostic performance of these imaging devices. RESULTS: At a fixed specificity of 84.2%, the sensitivity of HRT II was significantly different for varying disc sizes (P=0.0004). The sensitivities for dissimilar disc sizes were not significantly different for the GDx VCC (P=0.928) or Stratus OCT (P=0.381). Logistic marginal regression also showed that sensitivity of HRT II increased with increasing disc size, whereas sensitivity of OCT and GDx were independent of the disc size. The sensitivity of all 3 technologies increased with increasing disease severity (decreasing mean deviation). CONCLUSIONS: Optic disc size affects the diagnostic capability of HRT II but not that of GDx VCC or Stratus OCT. The sensitivity of all 3 imaging technologies increased with increasing disease severity.