OUTER RETINAL TUBULATION IN RETINAL DYSTROPHIES.

BACKGROUND/PURPOSE: To evaluate the occurrence and characteristics of outer retinal tubulation (ORT) in an Indian population with retinal dystrophies. METHODS: In this retrospective study, 309 eyes of 157 patients with retinal dystrophies including retinitis pigmentosa (RP, 183 eyes), Stargardt disease (STGD, 93 eyes) and Best disease (33 eyes) were reviewed. The demographic details, clinical data including visual acuity, treatment history and good quality spectral domain optical coherence tomography (SD-OCT) scans were collected. The characteristics of ORT including location, number, type, associated intraretinal fluid, disruption of outer retina and presence of other lesions were recorded. RESULTS: ORT was detected in 12 eyes of 8 patients (unilateral in 4 eyes). Their mean age was 42.5 ± 13.89 yrs. (range, 21-60 yrs.), the mean baseline best corrected visual acuity was 0.425 ± 0.7 LogMAR (Snellen equivalent 20/53) and the median follow up was 6 months. The frequency of ORT were; 6 out of 183 (3%) eyes in RP, 2 out of 93 (2%) eyes in STGD, and 4 out of 33 (12%) eyes with Best disease and this difference in frequency was found to be statistically significant (χ = 6.93, p = 0.03). The average number of ORT in each eye was 2.75 ± 2.0 and the mean height of ORT was 40.8 ± 15.4 µm. Three eyes had co-existing choroidal neovascularization. All eyes had tubular structures except one that had the branching type. The ORT in 2 eyes of one patient with Best disease who had 3 years follow up data was found to be stable over the entire period. CONCLUSION: ORTs are present in patients with RP, STGD and Best disease with a higher frequency in Best disease.

Melanopsin Cell Dysfunction is Involved in Sleep Disruption in Parkinson's Disease.

BACKGROUND: Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) signal the environmental light to mediate circadian photoentrainment and sleep-wake cycles. There is high prevalence of circadian and sleep disruption in people with Parkinson's disease, however the underlying mechanisms of these symptoms are not clear. OBJECTIVE: Based on recent evidence of anatomical and functional loss of melanopsin ganglion cells in Parkinson's disease, we evaluate the link between melanopsin function, circadian, and sleep behavior. METHODS: The pupil light reflex and melanopsin-mediated post-illumination pupil response were measured using chromatic pupillometry in 30 optimally medicated people with Parkinson's disease and 29 age-matched healthy controls. Circadian health was determined using dim light melatonin onset, sleep questionnaires, and actigraphy. Ophthalmic examination quantified eye health and optical coherence tomography measured retinal thickness. RESULTS: The melanopsin-mediated post-illumination pupil response amplitudes were significantly reduced in Parkinson's disease (p < 0.0001) and correlated with poor sleep quality (r2 = 33; p < 0.001) and nerve fiber layer thinning (r2 = 0.40; p < 0.001). People with Parkinson's disease had significantly poorer sleep quality with higher subjective sleep scores (p < 0.05) and earlier melatonin onset (p = 0.01). Pupil light (outer retinal) response metrics, daily light exposure and outer retinal thickness were similar between the groups (p > 0.05). CONCLUSION: Our evidence-based data identify a mechanism through which inner retinal ipRGC dysfunction contributes to sleep disruption in Parkinson's disease in the presence of normal outer retinal (rod-cone photoreceptor) function. Our findings provide a rationale for designing new treatment approaches in Parkinson's disease through melanopsin photoreceptor-targeted light therapies for improving sleep-wake cycles.

Outer Retinal Structure and Function Deficits Contribute to Circadian Disruption in Patients With Type 2 Diabetes.

Purpose: Light transmitted by retinal photoreceptors provides the input for circadian photoentrainment. In diabetes, there is a high prevalence of circadian and sleep disruption but the underlying causes are not well understood. Patients with diabetes can exhibit dysfunctional photoreceptors but their role in circadian health is not known. Here we quantify photoreceptor function and contributions to circadian health and sleep in patients with diabetes without diabetic retinopathy and healthy controls. Methods: Rod, cone, and melanopsin function was derived using chromatic pupillometry in 47 participants including 23 patients with type 2 diabetes and 24 age-matched healthy controls after an ophthalmic examination including retinal thickness assessment using optical coherence tomography. Circadian health was determined using dim light melatonin onset (DLMO) and sleep questionnaires; light exposure was measured using actigraphy. Results: Compared with the control group, the patients with diabetes had a significantly earlier DLMO (1 hour) (P = 0.008), higher subjective sleep scores (P < 0.05), a reduction in pupil constriction amplitude for red stimuli (P = 0.039) and for the early postillumination pupil response (PIPR) for blue (P = 0.024) stimuli. There were no between-group differences in the light exposure pattern, activity levels, and intrinsic melanopsin-mediated PIPR amplitude (P > 0.05). A significant correlation was evident between outer retinal thickness and DLMO (r = -0.65, P = 0.03) and the pupil constriction amplitude (r = 0.63, P = 0.03); patients with thinner retina had earlier DLMO and lower pupil amplitudes. Conclusions: We infer that the observed changes in circadian function in patients with no diabetic retinopathy are due to structural and functional outer retinal rod photoreceptor deficits at early stage of diabetic eye disease.

Evaluation of Choroidal Layer Thickness in Central Serous Chorioretinopathy.

PURPOSE: To evaluate medium and large choroidal vessel layer thickness (MCVT and LCVT, respectively) in eyes with acute and chronic central serous chorioretinopathy (CSC) in comparison with age-matched controls. METHODS: The study included 96 eyes of 96 patients with CSC, including 53 eyes with acute CSC, 43 eyes with chronic CSC, and 30 eyes of 30 age-matched normal subjects. Manual measurements of subfoveal choroidal thickness (SFCT), MCVT, and LCVT at subfoveal and 750 µm nasal and temporal to the fovea locations were made on enhanced depth imaging optical coherence tomography (EDI-OCT) of the macula in all subjects using ImageJ software (National Institutes of Health, Bethesda, MD, USA). RESULTS: SFCT in acute CSC was significantly larger than that in healthy eyes (P = 0.0001). SFCT in acute CSC did not differ significantly from that in chronic CSC eyes. Subfoveal LCVT and MCVT in acute CSC eyes were greater than those in healthy eyes (P = 0.02 and P = 0.03, respectively). Mean SFCT and MCVT in chronic CSC eyes were significantly larger than those in control eyes (P = 0.01 and P = 0.04, respectively). No significant difference in LCVT was observed between chronic and control eyes. CONCLUSION: Choroidal vasculature is altered in both acute and chronic CSC. SFCT, MCVT, and LCVT are higher in eyes with acute CSC. The thickening of medium choroidal vessels is still detectable in chronic CSC compared to control eyes.

Focal Choroidal Excavation in Retinal Dystrophies.

AIM: To investigate the presence of focal choroidal excavation (FCE) in patients with retinitis pigmentosa (RP), Stargardt's disease (STGD), and Best disease in the Indian population. METHODS: This retrospective consecutive case series included 309 eyes of 157 patients with RP (183 eyes), STGD (93 eyes), and Best disease (33 eyes) with good-quality, enhanced-depth spectral domain optical coherence tomography scans. Comprehensive ophthalmic examination data were collected. Characteristics of FCE, including location of FCE, type (conforming and non-conforming), maximal width, and depth, were noted. RESULTS: FCE was found in 2 out of 33 (6%) eyes with Best disease and no FCE was found in eyes with RP or STGD. The location of the FCE was extrafoveal in both cases. The first case had non-conforming FCE while the second case had the conforming type and the FCE occurred in association with choroidal neovascularization in the second case. The first case maintained good visual acuity of 20/20 over the entire period of follow-up (14 months), while the second case had a visual acuity of 20/200 at the last follow-up (three years) due to scarred choroidal neovascular membranes. The FCE showed no change in both eyes over the entire duration of follow-up. CONCLUSION: Focal choroidal excavation was found in 6% of eyes with Best disease, which remained stable throughout follow up. Eyes with RP and STGD did not have any FCE. Further studies are required to determine the role of vitelliform material in FCE development in Best disease.

Comparison of choroidal vessel thickness in children and adult eyes by enhanced-depth imaging optical coherence tomography imaging.

AIM: To evaluate choroidal thickness, medium choroidal vessel thickness (MCVT) and large choroidal vessel thickness (LCVT) in normal children and adult subjects. METHODS: Manual measurements of subfoveal choroidal thickness (SFCT), MCVT and LCVT at subfoveal and 750 µm nasal and temporal to fovea locations were completed on enhanced-depth imaging optical coherence tomography (EDI-OCT) scans of normal children and adult subjects. RESULTS: Fifty adult and fifty-seven child subjects were included in the study (including 80 adult and 103 child eyes). Mean (±SD) SFCT of adult and children eyes in the study was 309.3±95.7 µm and 279.3±50.4 µm respectively. SFCT and subfoveal MCVT in adult eyes were significantly more than children (P=0.01 and P≤0.0001 respectively). CONCLUSION: There is choroidal thickening with associated thickening of medium choroidal vessels in adults, suggesting that there is alteration in choroidal vasculature with ageing.

Segmentation errors in macular ganglion cell analysis as determined by optical coherence tomography in eyes with macular pathology.

BACKGROUND: To evaluate artifacts in macular ganglion cell inner plexiform layer (GCIPL) thickness measurement in eyes with retinal pathology using spectral-domain optical coherence tomography (SD OCT). METHODS: Retrospective analysis of color-coded maps, infrared images and 128 horizontal B-scans (acquired in the macular ganglion cell inner plexiform layer scans), using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). The study population included 105 eyes with various macular conditions compared to 30 eyes of 30 age-matched healthy volunteers. The overall frequency of image artifacts and the relative frequency of artifacts were stratified by macular disease. RESULTS: Scan errors and artifacts were found in 55.1% of the 13,440 B-scans in eyes with macular pathology and 26.8% of the 3840 scans in normal eyes. Segmentation errors were the most common scan error in both groups, with more common involvement of both segmentation borders in diseased eyes and anterior segmentation border in normal eyes. CONCLUSION: Segmentation errors and artifacts in SD OCT GCA are common in conditions involving the macula. These findings should be considered when assessing macular GCIPL thickness and careful assessment of scans is suggested.

Prevalence and Distribution of Segmentation Errors in Macular Ganglion Cell Analysis of Healthy Eyes Using Cirrus HD-OCT.

PURPOSE: To determine the frequency of different types of spectral domain optical coherence tomography (SD-OCT) scan artifacts and errors in ganglion cell algorithm (GCA) in healthy eyes. METHODS: Infrared image, color-coded map and each of the 128 horizontal b-scans acquired in the macular ganglion cell-inner plexiform layer scans using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) macular cube 512 × 128 protocol in 30 healthy normal eyes were evaluated. The frequency and pattern of each artifact was determined. Deviation of the segmentation line was classified into mild (less than 10 microns), moderate (10-50 microns) and severe (more than 50 microns). Each deviation, if present, was noted as upward or downward deviation. Each artifact was further described as per location on the scan and zones in the total scan area. RESULTS: A total of 1029 (26.8%) out of total 3840 scans had scan errors. The most common scan error was segmentation error (100%), followed by degraded images (6.70%), blink artifacts (0.09%) and out of register artifacts (3.3%). Misidentification of the inner retinal layers was most frequent (62%). Upward Deviation of the segmentation line (47.91%) and severe deviation (40.3%) were more often noted. Artifacts were mostly located in the central scan area (16.8%). The average number of scans with artifacts per eye was 34.3% and was not related to signal strength on Spearman correlation (p = 0.36). CONCLUSIONS: This study reveals that image artifacts and scan errors in SD-OCT GCA analysis are common and frequently involve segmentation errors. These errors may affect inner retinal thickness measurements in a clinically significant manner. Careful review of scans for artifacts is important when using this feature of SD-OCT device.