Neurosarcoidosis, Coccidioidomycosis, or Both!

Purpose: To report a case of neurosarcoidosis (NS) who was initially diagnosed as Coccidioidomycosis immitis (CI) infection. Observations: A 57-year-old diabetic man presented with sudden painless diminution of vision, metamorphopsia, and color vision deficits in the left eye (OS) for one month. His vision was 20/20 in the right eye (OD) and 20/40 OS. Ophthalmic examination revealed left relative afferent pupillary defect, blurred optic nerve margin, creamy chorioretinal infiltration around the optic disc, and mild macular edema. OD examination was non-revealing. Chest CT scan with contrast showed calcified mediastinal lymph nodes, but biopsy of the lymph nodes was normal. Brain and orbit MRI demonstrated soft tissue abnormality with enhancement in left orbital apex with involvement of the extraocular muscles. CSF culture was negative, but complement fixation had positive titer of 1:2 for CI. The patient was diagnosed with CI meningitis, and antifungal therapy was initiated. Slight visual and symptomatic improvement was observed, which was not completely satisfactory. Biopsy of extraocular orbital muscle five months later revealed non-caseating granulomatous inflammation, leading to initiation of prednisone trial therapy. Nine months later, the patient was referred to a tertiary center owing to persistence of optic disc edema OS. PET CT was consistent with a diagnosis of sarcoidosis. Antifungal treatment was discontinued, and oral prednisone with methotrexate was initiated. Subsequently, methotrexate was replaced by infliximab to further manage ocular inflammation and neurologic symptoms which was effective. Vision was 20/20 OD and 20/30 OS at the most recent visit. Conclusion and Importance: Signs and symptoms of neurosarcoidosis and coccidioidomycosis can be similar and deceiving. The index case underscores importance of considering appropriate differential diagnoses in patients with similar symptoms and signs who may respond to preliminary designated treatment but not to the optimal extent. Considering such possibility could assist clinicians in managing the patients timely and efficiently.

Effect of Pupil Size on Fixed-Luminance Flicker Full-Field Electroretinogram Magnitude.

Purpose: Diopsys® NOVA fixed-luminance flicker full-field electroretinogram (ffERG) device is a potential adjunct to conventional flicker ffERG testing for assessing cone cell function. Magnitude of measured electrical response is known to vary with pupil size in conventional ffERG testing. The index study characterizes the relationship between magnitude of measured electrical activity and pupil size, both pupil diameter and pupil area, for this device. Methods: Seventeen patients (34 eyes) with no known ocular diseases were enrolled in the study. Electrophysiologic function of cone cells was evaluated using fixed-luminance flicker ffERG before and after dilation. Linear regression models, with inter-eye correlations controlled as fixed-effects, were used to characterize the effect of pupil dilation on the magnitude of the measured responses. Results: Mean age of study patients was 33.5 (standard deviation 7.4 years), and 35.3% of the subjects were female. Mean value of electrical response magnitude was 10.07±2.79µV before dilation and 15.30±4.08µV after dilation. The correlations of ERG magnitude with pupil diameter and with pupil area were not significant for either dilated or undilated eyes considered separately but were highly significant (p<0.001) for dilated and undilated eyes considered in aggregate. ERG magnitude tended to increase by 1.08 µV for every 1 mm increase in pupillary diameter. Conclusion: An increase in pupil size, both pupil diameter and pupil area, is significantly associated with an increase in flicker ffERG magnitude recorded by the Diopsys device, suggesting that pupil size should be measured and considered when making clinical judgments based on the flicker ffERGs recorded by the device, and that pupil size-specific reference ranges could improve the clinical utility of the device.

CRB1-Related Leber Congenital Amaurosis: Reporting Novel Pathogenic Variants and a Brief Review on Mutations Spectrum

Background: LLeber congenital amaurosis (LCA) is a rare inherited retinal disease causing severe visual impairment in infancy. It has been reported that 9-15% of LCA cases have mutations in CRB1 gene. The complex of CRB1 protein with other associated proteins affects the determination of cell polarity, orientation, and morphogenesis of photoreceptors. Here, we report three novel pathogenic variants in CRB1 gene and then briefly review the types, prevalence, and correlation of reported mutations in CRB1 gene. Methods: Whole exome sequencing and targeted gene panel were employed. Then validation in the patient and segregation analysis in affected and unaffected members was performed. Results: Our detected novel pathogenic variants (p.Glu703*, c.2128+1G>A and p.Ser758SerfsX33) in CRB1 gene were validated by Sanger sequencing. Segregation analysis confirmed the inheritance pattern of the pathogenic variants. Conclusion: Our findings show that emerging the next-generation sequencing-based techniques is very efficient in identifying causative variants in disorders with locus heterogeneity.

Comparison of Intravitreal Bevacizumab and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity.

PURPOSE: To compare the outcomes of patients with type I retinopathy of prematurity (ROP) treated with either intravitreal bevacizumab (IVB) or retinal laser photocoagulation (RLP). DESIGN: Retrospective case series. PARTICIPANTS: Infants treated for type I ROP with IVB or RLP. METHODS: Patients who were born between January 2011 and December 2014 and were treated in Farabi Eye Hospital were included. The outcomes were stratified and analyzed, based on the treatment type and ROP zone. MAIN OUTCOME MEASURES: Need for retreatment, time to regression, refractive errors, retinal adverse anatomic outcomes, and rate of complications. RESULTS: Five hundred twenty-three patients were treated for type 1 ROP, of whom 493 (986 eyes) met inclusion criteria. Seven hundred twenty-four eyes (73.4%) received IVB, and 262 eyes (26.5%) received RLP. Re-treatment (because of recurrent or persistent retinopathy) occurred in 14.4% (106/724) of eyes initially treated with IVB and in 8.8% (23/262) eyes initially treated with RLP (P = 0.065). Re-treatment was not significantly different between the 2 groups for patients with zone I disease (P = 0.978). Re-treatment rate was considerably higher in patients with zone II disease treated with IVB (69/558 [12.3%]) compared with those treated with RLP (20/251 [7.9%]; P = 0.017). In the IVB group, 82.8% and 53.4% of eyes showed an avascular area in zone III (despite ROP regression) at 1 and 2 years after treatment, respectively. The spherical power and the spherical equivalent were significantly higher in eyes treated with RLP (-1.31±2.83 diopters [D] and -2.84±2.77 D, respectively) than eyes treated with IVB (0.19±3.21 D and -1.26±3.19 D, respectively; P = 0.016 and P = 0.007, respectively). Differences in astigmatic power were not significant. CONCLUSIONS: Both IVB and RLP are effective treatments for type 1 ROP. Longer follow-up time is necessary for infants treated with IVB. More patients with zone II disease treated with RLP achieved disease regression after a single treatment than those who received IVB, although outcomes after re-treatment were comparable except for a greater refractive error in patients treated with RLP.

Calcium dobesilate reduces endothelin-1 and high-sensitivity C-reactive protein serum levels in patients with diabetic retinopathy.

PURPOSE: To determine the benefits of calcium dobesilate (CaD) administration on endothelial function and inflammatory status in patients with diabetic retinopathy through measurement of serum levels of endothelin-1 and high-sensitivity C-reactive protein (hsCRP). METHODS: In a double-blind, randomized clinical trial, 90 patients with either severe nonproliferative or proliferative diabetic retinopathy and with blood glucose level of 120-200 mg/dl were randomly allocated to treatment with either CaD tablets (500 mg daily) or placebo for 3 months. Visual acuity, intraocular pressure, and macular status were performed before the study. The serum levels of endothelin-1 and hsCRP were evaluated in both groups before and at the third month of the trial. RESULTS: The median serum level of hsCRP significantly differed between the groups 3 months following the CaD or placebo administration (2.2 mg/l in the CaD group versus 3.7 mg/l in the placebo group, p=0.01). The mean endothelin-1 serum level was 0.69±0.32 pg/ml in the CaD group and 0.86±0.30 pg/ml in the placebo group (p=0.01). Furthermore, in the CaD group, the serum levels of both endothelin-1 and hsCRP were significantly decreased 3 months after administration of CaD (p<0.001). CONCLUSIONS: Administration of the CaD in the patients with diabetic retinopathy may reduce the serum levels of endothelin-1 and hsCRP. This might imply amelioration of the endothelial function and inflammatory status following CaD therapy in these patients.