Sourabh Sharma

Optical coherence tomography angiography in acute non-arteritic anterior ischaemic optic neuropathy

Purpose To characterise vascular changes in eyes with acute non-arteritic anterior ischaemic optic neuropathy (NAION), using optical coherence tomography angiography (OCT-A) imaging. Methods This hospital-based observational case-control study included included five patients with acute NAION (6 eyes), within 7 days after onset of symptoms and 19 age-matched healthy controls (19 eyes). OCT-A (RTVue XR 100; Optovue, Fremont, California, USA), covering a 4.5×4.5 mm scan area, was used to evaluate peripapillary blood flow in cases and controls. The flow densities at the retinal and choroidal level were measured using the split-spectrum amplitude-decorrelation angiography algorithm. Results The mean age of the NAION and normal subjects was 69 (61–82) and 68 (58–82) years, respectively (p=0.3). At the acute stage, OCT-A disclosed global reduction of the mean peripapillary flow density in eyes with NAION (53.5±3.7%) compared with normal eyes (64.3±2.4%) (p<0.001). The mean vascular flow density was also reduced in the peripapillary choroid layer of eyes with NAION (53.2±7.8%) compared with controls (69.5±3.0%) (p<0.001). In patients (3 eyes) with resolution of optic disc oedema, a repeated OCT-A analysis (at 4–22 weeks) of the full segment (including retina and choroid) revealed spontaneous improvement of the average total peripapillary flow density by 8.1±2.7%. Conclusions Using OCT-A, we revealed a global and sectorial reduction of retinal and choroidal peripapillary flow densities at the acute stage of NAION, followed by partial subsequent spontaneous recovery. Further studies are needed to establish the potential value of OCT-A for evaluating NAION and other optic neuropathies.

Shape Changes of the Anterior Lamina Cribrosa in Normal, Ocular Hypertensive, and Glaucomatous Eyes Following Acute Intraocular Pressure Elevation

Purpose The purpose of this study was to estimate and compare changes in anterior lamina cribrosa (LC) morphology in normal, ocular hypertensive (OHT), and glaucomatous eyes following acute elevations in intraocular pressure (IOP). Methods The optic nerve heads (ONHs) of 97 subjects (17 OHT, 19 primary open-angle glaucoma [POAG], 31 primary angle-closure glaucoma [PACG], and 30 normal subjects) were imaged using optical coherence tomography (OCT). Intraocular pressure was raised twice by applying forces to the anterior sclera, using an ophthalmodynamometer. After each IOP elevation, IOP was held constant and measured; each ONH was rescanned with OCT. In each OCT volume, the anterior LC was enhanced, delineated, and its global shape index (GSI) calculated and compared across groups. Results The baseline IOP was 17.5 ± 3.5 mm Hg and was increased to 38 ± 5.9 mm Hg and then to 46.5 ± 5.9 mm Hg. At the first IOP increment, mean GSI was significantly smaller than that at baseline in normal subjects and glaucoma subjects (P < 0.05) but not in OHT subjects (P = 0.12). For the second IOP increment, the mean GSI was significantly smaller than that at baseline in normal subjects and in OHT eyes (P < 0.05). After adjusting for age, sex, and baseline IOP, the LC of POAG eyes was found to be significantly more posteriorly curved than that of normal subjects (P = 0.04). Conclusions Acute IOP elevations altered anterior LC shape in a complex nonlinear fashion. The LC of POAG eyes was more cupped following acute IOP elevations compared to that of normal subjects.

Clinical effectiveness of brinzolamide 1%- brimonidine 0.2% fixed combination for primary open-angle glaucoma and ocular hypertension

The main first-line treatment strategy for glaucoma is to reduce intraocular pressure (IOP) by topical ocular hypotensive medications, but many patients require multiple medications for adequate IOP control. Fixed-combination therapies provide several benefits, including simplified treatment regimens, theoretical improved treatment adherence, elimination of the potential for washout of the first drug by the second, and the reduction in ocular exposure to preservatives. β-Adrenoceptor antagonists (particularly 0.5% timolol) are the most commonly used agents in combination with other classes of drugs as fixed-combination eyedrops, but they are contraindicated in many patients, owing to local allergy or systemic side effects. A fixed-combination preparation without a β-blocker is therefore warranted. This paper reviews the clinical effectiveness of brinzolamide 1% and brimonidine 0.2% fixed combination (BBFC) for use in patients with primary open-angle glaucoma and ocular hypertension. We searched PubMed and the ClinicalTrials.gov registry, and identified three randomized controlled trials comparing BBFC vs its constituents (brimonidine vs brinzolamide), and one comparing BBFC with unfixed brimonidine and brinzolamide. All of the studies demonstrated mean diurnal IOP to be statistically significantly lower in the BBFC group compared with constituent groups and noninferior to that with the concomitant group using two separate bottles. The safety profile of BBFC was consistent with that of its individual components, the most common ocular adverse events being ocular hyperemia, visual disturbances, and ocular allergic reactions. Common systemic adverse effects included altered taste sensation, oral dryness, fatigue, somnolence, and decreased alertness. BBFC seems to be a promising new fixed combination for use in glaucoma patients. However, long-term effects of BBFC on IOP, treatment adherence, and safety need to be determined.

Biometric Factors Associated With Acute Primary Angle Closure: Comparison of the Affected and Fellow Eye

Purpose To compare ocular biometric and anterior segment parameters between the affected and fellow eye in subjects with acute primary angle closure (APAC). Methods We evaluated 76 subjects with unilateral APAC who had undergone bilateral laser peripheral iridotomy before enrollment. Imaging was done using anterior segment optical coherence tomography and a customized software was used to measure the following: angle opening distance (AOD750); trabecular-iris space area (TISA750); iris thickness (IT750); iris curvature (ICURV); iris area (IAREA); anterior chamber depth; area and volume (ACD; ACA and ACV); anterior chamber width (ACW); anterior vault (ACD+LV); lens vault (LV); and pupil diameter (PD). We used A-scan ultrasonography to measure axial length (AL) and lens thickness (LT). Mean differences in ocular biometric and anterior segment parameters were assessed using linear mixed model adjusting for PD. Results A total of 53 subjects (36 females, 67.9%) with a mean age of 62.7 ± 8.1 years were analyzed after excluding 17 unanalyzable images in at least one eye. Affected eyes had shallower ACD, smaller ACA, ACV, anterior vault, TISA750, AOD750, and ICURV (all P < 0.05). Axial length, ACW, LV, LT, IAREA, and IT750 did not differ between the eyes. In the affected eyes, IT750 was significantly associated AOD750 (P < 0.05); whereas in the fellow eyes, IT750 and AL was predictive of AOD750 (all P < 0.05). Conclusions Eyes with previous APAC had smaller anterior segment dimensions when compared with their fellow eyes. Iris thickness was the strongest predictor of angle width in both affected and fellow eyes.

Effect of acute intraocular pressure elevation on the minimum rim width in normal, ocular hypertensive and glaucoma eyes

Background To estimate and compare changes in the Bruch’s membrane opening—minimum rim width (BMO–MRW) and area in normal, ocular hypertensive and glaucoma eyes following acute elevations in intraocular pressure (IOP). Methods The optic nerve heads (ONHs) of 104 subjects (31 normals, 20 ocular hypertension (OHT) and 53 with primary glaucoma) were imaged using Spectral-domain optical coherence tomography (OCT; Spectralis, Heidelberg Engineering, Germany). IOP was raised twice by applying a force (0.64 n then 0.9 n) to the anterior sclera using an ophthalmo-dynamometer. After each IOP increment, IOP was held constant, measured with a Tonopen (AVIA applanation tonometer, Reichert, Depew, New York, USA), and ONH was rescanned with OCT. In each OCT volume, BMO–MRW and area were calculated and at each IOP increment. Results The baseline MRW was significantly smaller in glaucoma subjects (174.3±54.3 µm) compared with normal (287.4±42.2 µm, p<0.001) and OHT subjects (255.4±45.3 µm, p<0.001). MRW of glaucoma subjects was significantly thinner at the first and second IOP elevations than that at baseline (both p<0.01), but no significant change was noted in normal and OHT subjects. There was no significant change of BMO area at acute IOP elevations from baseline in all diagnoses (all p>0.05). Conclusion Acute IOP elevation leads to compression of the nerve fibre layers of neuroretinal rim in glaucoma subjects only without changing ONH size. This suggests that the neural and connective tissues at ONH level in glaucoma subjects are more susceptible to acute IOP episodes than OHT or normal controls.

Disrupted Eye Movements in Preperimetric Primary Open-Angle Glaucoma

Purpose Primary open-angle glaucoma (POAG) can be associated with abnormal ocular motor behavior, possibly as a compensatory strategy following visual field loss. The aim of this study was to explore the characteristics of saccadic eye movements in patients with early-stage POAG without any detectable glaucomatous visual field loss (i.e., preperimetric POAG). Methods Binocular eye movements were explored in 16 patients with bilateral preperimetric POAG and 16 age-matched healthy controls in a cross-sectional, observational study. Visually guided horizontal prosaccades (5°, 10°, 15°, and 20° amplitude) and antisaccades (12° amplitude) were measured using infrared oculography. The latency, average and peak velocities, amplitude and gain of prosaccades as well as the percentage of errors in the antisaccades task were compared between groups. Results POAG patients exhibited a reduced average velocity of saccades compared to controls across all amplitudes of peripheral visual target presentation (P = 0.03). Saccades performed by POAG patients were hypometric, and with reduced amplitude (P = 0.007) and gain (P = 0.01) compared to controls. On average, POAG patients displayed more antisaccade errors (40.6%), as compared to controls (23.4%; P = 0.04). Conclusions Here, we show that patients with POAG without detectable glaucomatous visual field loss exhibit altered saccadic eye movements. These abnormalities may indicate disordered cortical and subcortical saccadic regulation, either on the basis of subthreshold visual impairment, or as a result of wider disease-associated neurodegeneration. Additional studies, controlling for glaucoma medications, are required to delineate the neural basis of eye movement abnormalities associated with POAG.

Pupillary responses to light are not affected by narrow irido-corneal angles

Chromatic pupillometry is an emerging method for evaluating ocular health that relies upon the differential stimulation of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Although it has been investigated in conditions affecting the outer or inner retina, there is a paucity of studies in conditions where the anterior chamber of the eye is affected. Primary angle closure suspects (PACS) are defined as eyes with narrow anterior chamber angles and intact retina. PACS patients are at risk of developing primary angle closure glaucoma and are prophylactically treated by performing laser peripheral iridotomy (LPI). Here we evaluated pupillary responses to monchromatic lights in 18 PACS before and after LPI, and compared the results with those of 36 age-matched controls who had gonioscopically open angles. Dose response curves for pupillary constriction were similar between PACS patients and controls (p = 0.98 for blue and 0.90 for red light) and within subjects pre- and post-LPI (p = 0.58 for blue and 0.20 for red light). Baseline-adjusted pupillary constriction responses to blue and red lights were similar in controls and PACS, and not altered after LPI. Our findings suggest that narrow irido-corneal angles and LPI do not influence pupillary responses in PACS.

OCT in Toxic and Nutritional Optic Neuropathies

Despite the recent developments of OCT in neuro-ophthalmology, its use for diagnosing and monitoring nutritional and toxic optic neuropathies is still limited, due to the lack of powered, longitudinal studies. Small series have suggested that OCT may be useful in various toxic optic neuropathies in the acute stage, disclosing subtle retinal nerve fibre layer thickening, ophthalmoscopically undetectable. At later stages, retinal nerve fibre layer thinning affects the papillomacular bundle, and then, all quadrants, but only rarely before visual loss. Macular volume OCT studies have suggested that in toxic optic neuropathies, the primary site of injury may involve the retinal ganglion cells layers. Retinal nerve fibre layer thinning in the nasal quadrant in patients treated with vigabatrin appears to be predictive of visual field constriction.