Botulinum toxin type A in multimodal management of age-related macular degeneration and related diseases.

Age related macular degeneration (AMD) is the major cause of visual loss in the aging population in the Western world. In past decade, intra ocular injections of anti-vascular endothelial growth factor (anti-VEGF) pharmaceuticals have revolutionized therapy for exudative (edematous-wet) AMD and become standard practice for the near term. However repeated intra-ocular injections are required for years and long terms results have been limited. The pathogenesis of this condition is multifactorial involving genetic, ischemic, inflammatory factors leading to neovascularization, edema and retinal pigment epithelial scaring resulting in photoreceptor destruction. Based on coincidental observation in reduction in AMD related macular edema on ocular coherence tomography (OCT) in a BoNT A treated patient with facial movement disease, BoNT-A at conventional doses targeting the para orbital area was added to therapeutic regiment in a small number of patients with exudative macular degeneration or related diseases. Measurements of edema and choriocapillaris using Spectral Doman (OCT) and Ocular Coherence Angiography (OCT-A) and Snellen visual acuity were made over the evaluation period. 15 eyes in 14 patients averaged 361 µm central sub foveal edema (CSFT) pre injection and average of 266 µm (CSFT) post injection over an average of 21 months and 5.7 cycles using BoNT A alone at conventional doses (n = 86 post injection measurements, paired t-test p < 0.001 two tailed). Visions at baseline in patients with 20/40 or worse averaged 20/100- pre injection improved to an average of 20/40- in the post injection period (n = 49 measurements p < 0.002 paired t-test). The previous data was added to a group of 12 more severely afflicted patients receiving anti VEGF (aflibercept or bevacizumab) (total 27 patients). With this 27-patient group, patients were followed for an average of 20 months and receiving average of 6 cycles at conventional doses. Improvement in exudative edema and vision were noted with pre injection baseline CSFT average 399.5, post injection average 267, n = 303 post measurement, independent t-test P < 0.0001.). Snellen vision 20/128 baseline average improved to average of 20/60- during post injection period (n = 157 post injection measurements, p < 0.0001 paired t-test to baseline). No substantial adverse effects were noted. Cyclic effects were noted corresponding to duration of action of BoNT-A on a number of patients. The above data is preliminary and is skewed toward early leakage for all conditions. BoNT A may have a role in the treatment of aged related macular degeneration. Controlled studies are needed with careful staging and baseline stratifications for multi-modal management paradigms. The findings are discussed relative to known botulinum toxin type A pharmacology and AMD pathogenesis.

Structural and functional phenotypic features and molecular analysis of Indian patients with Bietti crystalline dystrophy.

Purpose: Bietti crystalline dystrophy (BCD) is a rare retinal dystrophy, uncommon in Indians. This study describes the various phenotypic features seen in the Indian population. Methods: In this retrospective, descriptive case series, records of patients with either clinical or molecular diagnosis of BCD from 2009 to 2020 were perused. Phenotypic and genotype information was collected and analyzed. Results: This study included 58 patients of BCD (31 males) aged 21-79 years (mean: 47 ± 14 years). The age at onset ranged from 7 to 41 years (mean: 28.8 ± 5.1 years). Vision ranged from 20/20 to counting fingers. There were 18 (31%) patients with stage 1 with crystals and mild retinochoroidal atrophy, 22 (38%) with stage 2 with atrophy extending beyond arcades, and 18 (31%) with absent crystals and extensive atrophy of stage 3. Choroidal neovascular membrane was seen in four patients. The optical coherence tomography showed retinochoroidal thinning (84.6%), outer retinal tubulations (71.8%), and paradoxical foveal thickening with interlaminar bridges (7.7%). Electrophysiology and visual fields showed reduced responses in advanced retinochoroidal changes. Molecular confirmation was available in five patients; five mutations were seen in the CYP4V2. Conclusion: A wide variation is seen in the phenotypic picture of BCD. A molecular diagnosis is helpful in differentiating from other retinal dystrophies. The OCT shows the peculiar feature of the interlaminar bridge in early cases with photoreceptor loss. Further investigations into this OCT feature may provide insights into the pathogenesis of BCD. A genotype-phenotype correlation could not be done.

Ultra-wide field imaging of pigmented para-venous retino-choroidal atrophy.

OBJECTIVE: To describe the ultra-wide field imaging features of pigmented para-venous retino-choroidal atrophy. DESIGN: Retrospective review at a tertiary care centre. PARTICIPANTS: Eight eyes of five patients with pigmented para-venous retino-choroidal atrophy who presented to our retina clinic over last 2 years. METHODS: Retrospective review of ultra-wide field pseudo-colour and short wave autofluorescence imaging was performed. In vivo histology of the macula and areas of retino-choroidal atrophy was studied with swept source optical coherence tomography (SS-OCT). RESULTS: The median age was 40 years (range: 22-67 years). Best corrected visual acuity ranged from perception of light to 20/20. The para-venous retino-choroidal atrophy and pigment clumping not only involved the major arcade vessels but also extended into the peripapillary area and retinal periphery. The affected areas demonstrated hypoautofluorescence with sharp hyperautofluorescent borders. Macular atrophy, epiretinal membrane and optic disc pallor were noted in two eyes each. In all cases, the affected pigmentary area had disorganization of inner retinal layers, disruption of outer retinal layers and retinal pigment epithelium and markedly thinned out choroid on swept source optical coherence tomography. Concurrent involvement with retinitis pigmentosa in the fellow eye was noted in two patients. CONCLUSION: Ultra-wide field imaging of pigmented para-venous retino-choroidal atrophy sheds light onto the widespread retino-choroidal abnormalities. Concurrent disc and macular involvement may jeopardize the visual function. Pigmented para-venous retino-choroidal atrophy may be considered as a self-limited form of retinitis pigmentosa.

Comparison of macular choroidal thickness among patients older than age 65 with early atrophic age-related macular degeneration and normals.

PURPOSE: To compare macular choroidal thickness between patients older than 65 years with early atrophic age-related macular degeneration (AMD) and normals. METHODS: This was a consecutive, cross-sectional observational study. Enhanced depth imaging spectral-domain optical coherence tomography using horizontal raster scanning at 12 locations throughout the macula was performed in one eye of consecutive patients presenting with large soft drusen alone, drusen with additional features of early AMD, or a normal fundus. Choroidal thickness was measured at 7 points for each raster scan in the central 3 mm of the macula (total 84 points per eye). In addition, a single subfoveolar measurement was obtained for each eye. RESULTS: One hundred fifty eyes of 150 patients were included. There was no significant difference between mean refractive error for each diagnosis category via one-way ANOVA (P = 0.451). Mean macular choroidal thickness (CT) was 235 ± 49 µm (range, 125-334 µm; median 222 µm) for normals, 161 ± 39 µm (range, 89-260 µm; median = 158 µm) for the drusen group, and 115 ± 40 µm (range, 22-256 µm; median = 112 µm) for patients with AMD. Mean macular CT was significantly different via one-way ANOVA among all diagnosis categories (P < 0.001). CONCLUSIONS: The presence of features of early AMD without geographic atrophy and/or soft drusen alone is associated with decreased mean macular CT in vivo compared to that in patients with no chorioretinal pathology. Using enhanced depth imaging, measurement of a single subfoveolar choroidal thickness is highly correlated to mean central macular CT.

Atrofia coroidea relacionada con la edad en pacientes hispanos: serie de casos / Age-related choroidal atrophy in hispanics patients: a case series

Propósito: describir los hallazgos y la medición del grosor coroideo subfoveal utilizando tomografía óptica coherente de imagen de profundidad mejorada (EDI OCT), en paciente hispanos con sospecha clínica de atrofia coroidea relacionada con la edad (ARCA). Métodos: estudio descriptivo y trasversal en 17 pacientes con impresión clínica de ARCA, basados en: disminución de la agudeza visual de reciente aparición, alteraciones pigmentarias en la macula, apariencia de fondo de ojo atigrado y atrofia peripapilar a pesar de no ser miope. A todos se les realizó examen oftalmológico completo, que incluía: Agudeza visual mejor corregida (BCVA), biomicroscopía con lámpara de hendidura y evaluación del fondo de ojo bajo dilatación. A estos pacientes se les realizó fotografía digital del fondo de ojo y tomografía óptica coherente de imagen de profundidad mejorada (EDI OCT). Se realizó un total de 5 mediciones del grosor coroideo en el área macular en cada ojo. Resultados: se evaluaron 26 ojos de 14 pacientes, con una edad media de 70,86 años (DS± 8,46 años). El 57.14% fueron mujeres y el 42.86% hombres. El promedio de la agudeza visual fue 20/47 (0,38 LogMAR), el 80.2% presentaron manifestación binocular. La media del grosor coroideo fue 119,53 µm (DS±49,68µm). No hubo correlación estadísticamente signifi cativa entre la BCVA y grosor coroideo (P=0.407). Conclusión: la atrofia coroidea relacionada con la edad es una condición que puede presentarse en pacientes hispanos de edad avanzada. Afecta igualmente a hombres y mujeres, es usualmente bilateral y el grado de adelgazamiento de la coroides no predice la agudeza visual final.

Purpose: to describe the findings and measure the subfoveal choroidal thickness with Enhanced Depth Imaging (EDI) OCT in hispanics subjects with clinical impression of age-related choroidal atrophy (ARCA). Methods: a descriptive and cross-sectional study of 17 subjects with clinical impression of ARCA: based on recently decreased visual acuity, pigmentary alterations in the macula, a tessellated fundoscopic appearance, and peripapillary atrophy despite being not myopic. All patients had a comprehensive ocular examination, including BCVA, biomicroscopic and fundus examination. They underwent color fundus photography and EDI OCT. A total of 5 measurements were took of each eye. Results: twenty six eyes were included from 14 patients, with a mean age 70,86 years (SD ± 8,46 years). The 57,14% were female and 42.86% male. The mean visual acuity was 20/47 (0,38 LogMAR Equivalent), 80.2% had bilateral disease. The mean choroidal thickness was 119,53 µm (SD ± 49,68 µm). There was no statistically significant correlation between BCVA and choroidal thickness (p =0,407). Conclusions: the ARCA is a condition that can be present in elderly Hispanics subjects. Affects equally male and female, it is usually bilateral and the degree of choroidal thinning does not predict the final visual acuity.