Understanding falls and its prevention among adults with visual impairment through behavior change models.

SIGNIFICANCE: This study used behavior change models to understand the perspectives of falls among patients with visual impairment who are at greater risk of falls. Resulting themes on barriers and facilitators led to the identification of a "SMART" intervention strategy that remains to be tested as a fall-reducing behavior. PURPOSE: This study explored the perspectives of adults with visual impairment on falls and proposed falls prevention strategies using behavior change models. METHODS: Participants 18 years or older who were diagnosed with low vision or blindness from a tertiary eye hospital in India and had a history of falls in the previous year were recruited. "Reduction of falls" was defined as a behavior, and interview questions were designed to explore awareness, context, and consequences of falls to determine barriers and facilitators that could help reduce falls. The interviews were audio-recorded, transcribed, translated into English, and analyzed using thematic analysis. The results were linked to the Theoretical Domains Framework and the Behavior Change Wheel, under different levels of a The Socio-Ecological Model. Intervention functions from the Behavior Change Wheel were identified using the APEASE criteria (affordability, practicability, effectiveness/cost-effectiveness, acceptability, safety/side effects, and equity) to finalize behavior change techniques. RESULTS: Themes on barriers and facilitators at individual, family, and societal levels were identified from 36 semistructured telephone interviews. Key barriers were fear of falling, social stigma and lack of training in using assistive devices, not considering falls as a major concern, environmental hazards, and loss of support from caregivers. Key facilitators were consciously monitoring falls, undergoing orientation and mobility training, getting assistance for outdoor mobility, and self-confidence. CONCLUSIONS: This study proposed a five-step "SMART" intervention strategy for prevention of falls to be prospectively tested. SMART include Support from caregivers and use of assistive devices, Monitoring of falls, Awareness about falls, Reduction of hazards, and Training for safe mobility.

Choriocapillaris flow deficits in polypoidal choroidal vasculopathy using swept source optical coherence tomography angiography.

Purpose: To evaluate the choriocapillaris flow deficits (CCFD) on swept-source optical coherence tomography angiography (SS-OCTA) in eyes with unilateral polypoidal choroidal vasculopathy (PCV), fellow unaffected eyes, and to compare them with age-matched healthy controls. Methods: This study was a cross-sectional study which included treatment-naïve eyes with unilateral PCV (group 1), fellow unaffected eyes of patients with PCV (group 2), and normal eyes (group 3). Using the SS-OCTA, the Choriocapillaris (CC) slab was segmented from the structural optical coherence tomography (OCT) and the corresponding flow map was multiplied after signal compensation. The resultant image was evaluated for CCFD in equidistant squares measuring 1 × 1 mm, 1.5 × 1.5 mm, 2 × 2 mm, 2.5 × 2.5 mm, 3 × 3 mm, and 6 × 6 mm centered on the fovea. Results: The percentage of flow deficits were significantly increased (one-way ANOVA, P = 0.003 and P = 0.049) in the eyes with PCV as compared to the fellow eyes, and age-matched healthy controls. In the multiple pairwise comparison using post hoc Bonferroni, CCFD of 1 mm in group 1 and 2 (P = 0.019), group 1 and 3 (P = 0.003), and CCFD of 1.5 mm in group 1 and 3 (P = 0.044) were statistically significant. Correlation analysis showed no significant correlation between CCFD, age, Best corrected visual acuity (BCVA), foveal thickness (FT), and subfoveal choroidal thickness (SFCT) in our study. Linear regression analysis showed that the CCFD was negatively correlated with the distance from the foveal center in group 1 (ß = -0.613, P = 0.046). Conclusion: Eyes with PCV demonstrated a significant flow impairment in the choriocapillaris layer as compared to the fellow unaffected eyes and age-matched healthy eyes.

Structural and functional changes among diabetics with no diabetic retinopathy and mild non-proliferative diabetic retinopathy using swept-source optical coherence tomography angiography and photopic negative response.

PURPOSE: To assess the structural and functional changes among diabetics with no diabetic retinopathy (NDR) and mild non-proliferative diabetic retinopathy (NPDR) using swept-source optical coherence tomography angiography (SSOCTA) and photopic negative response (PhNR) and to find the earliest changes. METHODS: This was a prospective, cross-sectional, case-control study. Participants with minimum 5 years of diabetes mellitus (DM) were recruited and classified as NDR and mild NPDR based on fundus findings. Age-matched normals with nil ocular pathology were considered as controls. SSOCTA scan acquisition (6*6 mm angiography), followed by full field photopic electroretinography (FFERG) and red on blue PhNR (R/B PhNR) were done with complete pupillary dilatation. RESULTS: A total of 88 participants were included with 35 controls, 39 NDR and 14 mild NPDR subjects. Vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) of mild NPDR were significantly reduced compared to the controls (17.12 ± 2.65 mm-1 vs. 18.75 ± 0.90 mm-1, p = 0.025 and 7.96 ± 3.92 mm-1 vs. 11.83 ± 3.05 mm-1, p = 0.001 respectively). None of the parameters of controls had significant difference compared to NDR group (p > 0.05). The amplitudes of white on white (W/W) a-wave, W/W b-wave, red on blue (R/B) PhNR baseline to trough (BT) and R/B PhNR peak to trough in controls were significantly high compared to NDR and mild NPDR. Amplitude of R/B PhNR BT had the maximum area under the curve of 75.9% with a sensitivity and specificity of 94.3and 77.4%, respectively. CONCLUSION: A significant decrease in functional changes as measured by ERG especially PhNR, is seen even among the NDR group compared to controls unlike SSOCTA parameters that measures very early vascular structural changes. PhNR is a sensitive test to identify early preclinical changes in DR when microvascular structural changes as determined by SSOCTA are normal.

Retino-choroidal evaluation of the macular region in eyes with tubercular serpiginous-like choroiditis using swept-source optical coherence tomography angiography.

AIM: To analyse the alterations in retino-choroidal angioarchitecture in eyes with active tubercular serpiginous-like choroiditis (TB-SLC) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: This prospective cross-sectional study enrolled 34 eyes diagnosed with TB-SLC and 34 age-matched healthy controls. Data acquisition with SS-OCTA using the PLEX Elite 9000 (Carl Zeiss Meditec Inc., Dublin, CA, USA) with a 6 × 6 mm pattern centered on the foveal center was done. Automated retinal vessel length density (VLD) and perfusion density (PD) and foveal avascular zone architecture were obtained from the ARI hub. Choroidal vascularity index (CVI) and choriocapillaris flow deficits (CCFD) were obtained using Image J. RESULTS: Eyes with TB-SLC showed significantly reduced vessel indices in all retinal layers (P < 0.05), decreased CVI (P = 0.001) and increased CCFD (P = 0.001) as compared to healthy eyes. CCFD was increased significantly in the involved quadrants in eyes with TB-SLC when compared with the uninvolved quadrants and corresponding healthy quadrants in control subjects. CCFD showed a significant negative correlation with visual acuity (r = - 0.46, P = 0.006). CONCLUSION: Eyes with TB-SLC manifest reduced VLD and PD, decreased CVI and increased CCFD. The CCFD alterations are non-uniform in these eyes, mainly located under the regions with disease activity.

Comparison of broadband and monochromatic photopic negative response in eyes of patients with diabetes with no diabetic retinopathy and different stages of diabetic retinopathy.

PURPOSE: To evaluate the change in broadband (W/W), red on blue (R/B), and blue on yellow (B/Y) photopic negative response (PhNR) in patients with diabetes mellitus with no diabetic retinopathy (no DR) and different stages of DR and compare it with age-matched controls. This study was performed to provide a single PhNR protocol that can be used for early diagnosis of DR. METHODS: It was a cross-sectional case-control study done in a hospital setup. Patients with diabetes with no DR and different stages of DR with no other associated ocular pathologies were included. Age-matched controls with no retinal pathologies were also included for comparison. All subjects underwent detailed ophthalmic examination and W/W, R/B, and B/Y electroretinography. Fifty control eyes and 52 treatment naïve eyes of 52 patients with diabetes [no DR = 11, mild nonproliferative diabetic retinopathy (NPDR) =11, moderate NPDR = 10, severe NPDR = 9, and proliferative DR = 11] were included in the study. RESULTS: On comparing the ERG responses in patients with diabetes and age-matched controls, a significant reduction (P < 0.05) was noted in the amplitudes of a-wave (39.78 ± 11.34 µV vs. 67.28 ± 12.88 µV), b-wave (116.25 ± 45.25 vs. 134.39 ± 28.78 µV), W/W PhNR (33.86 ± 17.33 vs. 67.18 ± 15.99 µV), R/B PhNR (28.77 ± 15.85 vs. 53.48 ± 14.15 µV), and B/Y PhNR (55.04 ± 32.63 vs. 104.79 ± 24.37 µV). Post hoc analysis revealed that all the eyes in the diabetic group, including those with no DR, had a significantly reduced PhNR amplitude (P < 0.05) when compared with controls. PhNR was found to reduce in amplitude with increasing severity of DR (P < 0.05), with more significance in B/Y. Receiver operating characteristic showed highest area under the curve in B/Y PhNR (94%, P < 0.001), with maximum sensitivity and specificity of 88% and 87%, respectively. CONCLUSION: Changes in the amplitude and implicit time of ERG can reflect the severity of DR. PhNR amplitudes, especially B/Y PhNR, appear to be significantly reduced even in eyes with no DR.

Comparison between broadband and monochromatic photopic negative response in full-field electroretinogram in controls and subjects with primary open-angle glaucoma.

PURPOSE: A prospective, cross-sectional, case-control study was conducted to investigate the role of broadband and monochromatic photopic negative response (PhNR) of the full-field flash electroretinogram (ERG) in the evaluation of ganglion cell damage in primary open-angle glaucoma (POAG) subjects. METHODS: Subjects with POAG and age-matched normal subjects were recruited from the outpatient department of a tertiary eye care center in South India. A total of 25 patients with POAG and 50 age-matched normal subjects were recruited. ERG was recorded using broadband (3.5 cd.s/m2 white stimulus on 10 cd/m2 white background) and monochromatic (3.5 cd.s/m2 red stimulus on 10 cd/m2 blue background and 1 cd.s/m2 blue stimulus on 10 cd/m2 yellow background) stimuli. RESULTS: The reduction in PhNR amplitude in POAG compared to normal individuals was higher in red-on-blue PhNR [26.37 µV; p < 0.001, confidence interval (CI) 19.34 to 33.4] as compared to broadband stimuli (16.41 µV; p < 0.001, CI 8.68 to 24.13), and blue on yellow (21.96 µV; p < 0.001, CI 10.12 to 33.8). Red-on-blue PhNR amplitudes correlated better with mean deviation (MD; r = - 0.66, p < 0.05), pattern standard deviation (PSD; r = - 0.4, p = 0.04), visual field index (VFI; r = - 0.58, p < 0.05), and retinal nerve fiber layer thickness (r = - 0.67, p < 0.05) in comparison with broadband and monochromatic blue-on-yellow PhNR. Receiver operating characteristic curve revealed largest area under the curve (0.89) in red-on-blue PhNR compared to broadband (0.76) and blue on yellow (0.74). The sensitivity and specificity was also higher in red-on-blue PhNR (72% and 80%, respectively) as compared to the other stimuli (sensitivity and specificity of broadband 0.68 and 0.7, blue on yellow 0.64 and 0.7, respectively). CONCLUSION: Correlation of PhNR with Humphrey visual field parameters and retinal nerve fiber layer thickness showed that red-on-blue PhNR can be a useful additional tool for clinical assessment of retinal ganglion cell dysfunction in glaucoma patients. Red-on-blue PhNR was more sensitive as compared to white-on-white and blue-on-yellow PhNR in identifying ganglion cell dysfunction and correlates well with other structural and functional tests for glaucoma such as MD, PSD, VFI, and RNFL thickness.

Swept-source optical coherence tomography study of choroidal morphology in Stargardt disease.

BACKGROUND: Stargardt disease, a juvenile retinal dystrophy, may show secondary changes in the choroid which may have importance while considering future treatments such as stem cell transplant. OBJECTIVE: To evaluate the choroidal and retinal morphology in patients with Stargardt disease and compare with age-matched normals. SETTING AND DESIGN: This was a case-control study at a tertiary level eye care institute. METHODS: Twenty-six patients (52 eyes) clinically diagnosed with Stargardt disease underwent detailed evaluation with swept-source optical coherence tomography. Retinal and choroidal layers were analyzed and compared with 52 eyes of controls. RESULTS: The median age of patients with Stargardt disease was 23 years. The mean best-corrected visual acuity was 0.82 logMAR (20/125 Snellen). Mean diameter of the lesion was 2810.92 ± 1311.15 µ. The lesion size increased with increasing extent of flecks and was significantly correlated with visual acuity (r = 0.622, P < 0.001). The retinal and choroidal thicknesses (CTs) were significantly reduced in Stargardt group. The mean subfoveal CT was 290.59 ± 60.43 µ(range: 184-395) in Stargardt and 331.31 ± 68.90 µ (range: 199-464) in normal group, P = 0.043. CT in Early Treatment Diabetic Retinopathy Study grid pattern showed significant thinning in Stargardt group. The small choroidal vessel (SCV) layer was more affected than the large choroidal vessel (LCV) layer. There was thinning of SCV and thickening of LCV inside the macular lesion. The CT was not correlated to lesion size, extent of flecks, or visual acuity. CONCLUSIONS: Stargardt disease shows generalized thinning of the choroid affecting mainly the SCVs. In the macular lesion, there is atrophy of SCV with compensatory dilation of LCV. The visual acuity did not correlate with CT but showed worsening with increasing lesion size and wider extent of flecks.

Understanding variable disease severity in X-linked retinoschisis: Does RS1 secretory mechanism determine disease severity?

X-linked retinoschisis (XLRS) is a retinal degenerative disorder caused by mutations in RS1 gene leading to splitting of retinal layers (schisis) which impairs visual signal processing. Retinoschisin (RS1) is an adhesive protein which is secreted predominantly by the photoreceptors and bipolar cells as a double-octameric complex. In general, XLRS patients show wide clinical heterogeneity, presenting practical challenges in disease management. Though researchers have attempted various approaches to offer an explanation for clinical heterogeneity, the molecular basis has not been understood yet. Therefore, this study aims at establishing a link between the phenotype and genotype based on the molecular mechanism exerted by the mutations. Twenty seven XLRS patients were enrolled, of which seven harboured novel mutations. The mutant constructs were genetically engineered and their secretion profiles were studied by in vitro cell culture experiments. Based on the secretory profile, the patients were categorized as either secreted or non-secreted group. Various clinical parameters such as visual acuity, location of schisis, foveal thickness and ERG parameters were compared between the two groups and control. Although the two groups showed severe disease phenotype in comparison with control, there was no significant difference between the two XLRS groups. However, the secreted group exhibited relatively severe disease indications. On the other hand molecular analysis suggests that most of the RS1 mutations result in intracellular retention of retinoschisin. Hence, clinical parameters of patients with non-secreted profile were analyzed which in turn revealed wide variability even within the group. Altogether, our results indicate that disease severity is not merely dependent on secretory profile of the mutations. Thus, we hypothesize that intricate molecular detail such as the precise localization of mutant protein in the cell as well as its ability to assemble into a functionally active oligomer might largely influence disease severity among XLRS patients.

Effect of axial length on full-field and multifocal electroretinograms.

PURPOSE: The aim was to investigate the effect of axial length on full-field electroretinogram (ffERG) and multifocal electroretinogram (mfERG) in young Indian subjects. METHODS: One hundred subjects (44 male) with refractive errors from +0.50 to -18.00 DS and no myopic retinopathy underwent axial length measurement. ffERG was measured, which included scotopic and photopic responses according to International Society for Clinical Electrophysiology of Vision (ISCEV) guidelines. The mfERG was recorded after correcting for refractive error according to ISCEV standards. The dark-adapted and light-adapted parameters of ffERG and N1, P1 parameters of six rings in mfERG were analysed with axial length, controlled for refractive error. The subjects were divided into seven groups based on axial length. The b/a ratio of dark-adapted and light-adapted 3.0 ffERG and P1/N1 ratio of mfERG amplitudes were analysed for seven groups of axial length. RESULTS: The axial length ranged from 21.79 to 30.55 mm. Significant negative correlations were noted for ffERG and mfERG amplitudes, whereas implicit times showed minimal delay with increase in axial length. In ffERG, the scotopic responses were more decreased compared to photopic responses. In mfERG, P1 and N1 amplitudes were significantly decreased in all the rings in all groups and more reduction was noted in the central ring compared to peripheral rings. The P1 amplitudes were more affected as compared to N1 amplitudes. The light-adapted and dark-adapted 3.0 ERG b/a ratio and P1/N1 ratio for seven axial length groups did not show statistically significant difference. The ERG parameters were not significant with refractive error. CONCLUSION: This study quantifies the relationship of axial length with ffERG and mfERG parameters in a young Indian population. Although the amplitudes were reduced significantly, the implicit times were not significantly affected. The ERG parameters were more related to axial length than refractive error. Hence, interpretation of ffERG and mfERG parameters needs careful consideration in subjects with increasing axial length.

Reduced-fluence photodynamic therapy and anti-vascular endothelial growth factor for polypoidal choroidal vasculopathy in an Indian population.

AIMS: The aim was to study the efficacy of combined therapy with reduced-fluence photodynamic therapy (RFPDT) and intravitreal bevacizumab/ranibizumab from the Indian subcontinent. SETTINGS AND DESIGN: This was a single-center, retrospective interventional study. METHODS: Thirty-five eyes of 34 patients diagnosed with polypoidal choroidal vasculopathy were included. All the patients underwent RFPDT, followed by intravitreal bevacizumab/ranibizumab. STATISTICAL ANALYSIS USED: SPSS software, version 17.0 (SPSS Inc., Chicago, IL, USA) was used to compare the logarithm of the minimal angle of resolution visual acuity at presentation and final follow-up. P< 0.05 was considered statistically significant. RESULTS: Regression of polyps after a single session of RFPDT was seen in five eyes; multiple sessions of treatment were required in thirty eyes. An average number of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections given were 4 ± 1.9 and average number of PDT sessions were 1.2 ± 0.5. Visual acuity improvement was seen in 21 (60%) eyes (P < 0.001), decrease in visual acuity was seen in 7 (20%) eyes (P = 0.016), and in 7 eyes (20%), vision remained stable. Regression of polypoidal lesions was seen in 80% of cases. No complications of massive subretinal hemorrhage or breakthrough vitreous hemorrhage were noted in our patients. The mean follow-up period was 18 months (range, 12-24 months). CONCLUSIONS: RFPDT with anti-VEGF is safe and effective treatment with polyp regression and vision improvement in 80% of cases, without any complication of subretinal hemorrhage/vitreous hemorrhage.

Comparison between fullfield electroretinography obtained from handheld and tabletop devices in normal subjects.

OBJECTIVE: To compare full-field electroretinography (ERG) parameters obtained from Ephios handheld and VERIS tabletop ERG devices in normal subjects for interchangeable usability and reliability. DESIGN: Comparison study. PARTICIPANTS: Comparison of full-field ERG between two devices for 57 normal subjects. METHODS: ERG was recorded for 57 normal subjects using tabletop device (VERIS 5.2.2X; Electro-Diagnostic Imaging Inc, San Mateo, Calif.) and handheld ERG device (Ephios handheld portable ERG system; ephios ab; Teknikringen, Linkoping, Sweden). Bland-Altman plot was done to measure the agreement between the 2 devices. Intraclass correlation coefficient (ICC) was calculated for amplitudes, implicit times, and b/a ratio to assess the reliability. Coefficient of variation (CV = 100 × [standard deviation/mean]) with 95% CI was calculated to measure the variability between the devices. Wilcoxon sign rank test was used to assess the repeatability of the Ephios handheld device. RESULTS: The mean a-wave and b-wave amplitudes of dark-adapted 3.0 ERG for the tabletop were 220.3 ± 52.6 and 471.5 ± 84.3 µV, respectively, whereas the mean a-wave and b-wave amplitudes in the same scotopic setting for the handheld device were 152.6 ± 34.2 and 379.7 ± 75.9 µV, respectively. The values represent mean ± standard deviation. The ICC of b/a ratio was 0.660 between the devices. The amplitudes CV of tabletop and handheld ERG devices ranged from 17.9% to 29.1% and from 22.4% to 30.1%, respectively. CONCLUSIONS: The pattern of waveform of the Ephios handheld device is similar to the VERIS tabletop device. The ERG parameters showed variability between the 2 devices. Hence Ephios handheld ERG device can be used along with its normative data for measuring ERG. Because of variability, the devices cannot be used interchangeably.

Molecular profiling of complete congenital stationary night blindness: a pilot study on an Indian cohort.

PURPOSE: Congenital stationary night blindness (CSNB) is a non-progressive retinal disorder that shows genetic and clinical heterogeneity. CSNB is inherited as an autosomal recessive, autosomal dominant, or X-linked recessive trait and shows a good genotype-phenotype correlation. Clinically, CSNB is classified as the Riggs type and the Schubert-Bornschein type. The latter form is further sub-classified into complete and incomplete forms based on specific waveforms on the electroretinogram (ERG). There are no molecular genetic data for CSNB in the Indian population. Therefore, we present for the first time molecular profiling of eight families with complete CSNB (cCSNB). METHODS: The index patients and their other affected family members were comprehensively evaluated for the phenotype, including complete ophthalmic evaluation, ERG, fundus autofluorescence, optical coherence tomography, and color vision test. The known gene defects for cCSNB, LRIT3, TRPM1, GRM6, GPR179, and NYX, were screened by PCR direct sequencing. Bioinformatic analyses were performed using SIFT and PolyPhen for the identified missense mutations. RESULTS: All eight affected index patients and affected family members were identified as having cCSNB based on their ERG waveforms. Mutations in the TRPM1 gene were identified in six index patients. The two remaining index patients each carried a GPR179 and GRM6 mutation. Seven of the patients revealed homozygous mutations, while one patient showed a compound heterozygous mutation. Six of the eight mutations identified are novel. CONCLUSIONS: This is the first report on molecular profiling of candidate genes in CSNB in an Indian cohort. As shown for other cohorts, TRPM1 seems to be a major gene defect in patients with cCSNB in India.

Full-field electroretinography under general anesthesia in retinoblastoma.

PURPOSE: To investigate the electrical responses of the retina in retinoblastoma (RB), by recording full-field electroretinography (ERG) under general anesthesia. METHODS: The ERG was recorded using Ephios hand-held portable ERG system, according to International Standards for Clinical Electrophysiology of Vision. Forty-eight eyes of 43 cases and 33 eyes of 33 controls were enrolled. The cases were classified based on international intraocular retinoblastoma classification (IIRC). Forty-eight eyes of cases were divided into 30 cases with active RB and 18 cases with regressed RB. RESULTS: The amplitudes of a- and b-waves were decreased as compared to controls in all subgroups. The implicit times of all RB patients from group A to C differed statistically from controls (p value < 0.05) except for single-flash rod response. The ERG waveforms in group E eyes were non-recordable. The comparison of ERG parameters between active and regressed groups (IIRC groups A and B) was statistically insignificant. Single case follow-up of unilateral RB after systemic chemotherapy showed improvement in amplitudes compared to baseline parameters. CONCLUSIONS: Reduced amplitudes and delayed implicit times were noted in advanced disease. The ERG of RB cases did not follow any specific pattern of waveform. ERG appears to be a dynamic parameter to observe changes following treatment for RB. Although ERG is not a diagnostic test for RB, it can be used as a complementary test to assess the residual retinal function in RB eyes.