Dense Scotoma Research Articles

Complete retinal pigment epithelium and outer retinal atrophy: Is it really an end-stage atrophy?

Geographic atrophy (GA), a late manifestation of age-related macular degeneration (AMD), leads to irreversible vision loss. Early identification of precursor lesions, such as incomplete and complete retinal pigment epithelium and outer retinal atrophy (iRORA and cRORA), is crucial for predicting GA formation. The latter stage has been associated with irreversible and progressive changes, and the eventual development of a dense scotoma on the compromised area. We present an 80-year-old woman with AMD in both eyes, demonstrating progressive changes over a 2-year follow-up. While the right eye developed cRORA with vision decline, the left eye exhibited unexpected restoration of the outer retinal layers within the cRORA lesion. This finding challenges the notion of "end-stage atrophy" in GA development and highlights the potential reversibility of early atrophic lesions. Recognizing these dynamics has implications for the development of targeted therapies aimed at preserving vision in AMD's early stages.

Severity of Disorganization of Retinal Layers and Visual Function Impairment in Diabetic Retinopathy

To evaluate best-corrected visual acuity (BCVA), retina sensitivity (RS), and fixation impairment by microperimetry (MP) due to the presence and severity of disorganization of retinal inner and outer layers (DRIL/DROL) and ischemia in OCT/OCT angiography (OCTA) in diabetic retinopathy (DR). Retrospective case-control study. Seventy-six eyes (65 patients) with DR were analyzed. Major exclusion criteria were: center-involving diabetic macular edema (DME), significant media opacity, nondiabetic macular pathology, and active proliferative DR. Patients with DRIL and DROL within central 3 mm were enrolled as cases. Patients with DR and no retina disorganization were considered as controls. A detailed grading of MP and OCT/OCTA images using Image J software, and specific Image Manipulation Program was applied to colocalize the presence of retina disorganization and RS. Best-corrected visual acuity and RS were correlated with the disorganization of retina layers' characteristics and grading (grade 1-DRIL; grade 2-DROL; grade 3-DROL plus, with involvement of the ellipsoid zone). The same procedure of colocalization was applied to the vascular layers on OCTA using MATLAB. Correlation between BCVA and MP parameters with disorganization of retina layers grading and OCTA parameters. Best-corrected visual acuity, mean RS within 1 mm and central 3 mm (overall RS [oRS]), perfusion density, vessel density, and geometric perfusion deficit in intermediate and deep capillary plexuses were lower in cases versus controls (P < 0.001). Mean RS within 1 mm (21.4 decibels [dB] ± 2.4 vs. 13.8 dB ± 5.4, P= 0.002), oRS (22.0 dB ± 2.1 vs. 14.4 dB ± 4.6, P < 0.001), and BCVA (76.1 ± 7.4 vs. 61.2 ± 20.4 ETDRS letters; P= 0.02), had a significant decrease from grade 1 to grade 3 retina disorganization. Choriocapillaris flow voids (CC-FVs) increased from grade 1 to grade 3 (DROL plus) (P= 0.004). Overall retina sensitivity and CC-FV were identified as significant predictors of retina disorganization grade with an adjusted coefficient of determination, R2= 0.45. Cases had more dense scotomas (P= 0.03) than controls with a positive correlation between the worsening of fixation stability and the severity of DRIL/DROL (P= 0.04). Microperimetry and BCVA documented a reduction in visual function in patients with DR and disorganization of retina layers at different grades, with greater functional impairment when outer retina layers and photoreceptors are involved. The severity of retina disorganization and the presence of ischemia could serve as a potential biomarker of functional impairment. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Functional Evaluation of Retinal Pigment Epithelium and Outer Retinal Atrophy by High-Density Targeted Microperimetry Testing

Complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) on OCT imaging has recently been proposed to describe end-stage atrophy in age-related macular degeneration (AMD) by international consensus and expected to be associated with a dense scotoma, but such functional evidence is lacking. This study sought to examine the visual sensitivity defects associated with cRORA and to determine OCT features associated with deep defects. Observational study. Sixty eyes from 53 participants, including 342 microperimetry tests over 171 study visits. Participants underwent targeted high-density threshold-based microperimetry testing of atrophic lesions (with at least incomplete RPE and outer retinal atrophy [iRORA]) with a 3.5° diameter grid. The maximum extent of signs of atrophy for all lesions was graded on OCT imaging. Number of deep visual sensitivity defects (threshold ≤ 10decibels [dB]). Presence of choroidal signal hypertransmission ≥ 500 μm, complete RPE loss ≥250 μm, and inner nuclear layer and outer plexiform layer subsidence, and hyporeflective wedge-shaped band (defined as nascent geographic atrophy [nGA]) ≥ 500 μm (P ≤ 0.020), but not RPE attenuation or disruption (P ≥ 0.192), were all independently associated with a significant increase in the number of deep visual sensitivity defects ≤ 10 dB. Only cRORA lesions with hypertransmission ≥ 500 μm or complete RPE loss ≥ 250 μm, or with both of these features (P < 0.001), but not lesions with only hypertransmission 250-499 μm (P = 0.303), had significantly more deep visual sensitivity defects ≤ 10 dB compared with iRORA lesions. Lesions with nGA ≥ 500 μm, irrespective of the presence of hypertransmission ≥ 500 μm and/or complete RPE loss ≥ 250 μm, also showed a higher number of deep visual sensitivity defects ≤ 10 dB compared with lesions without nGA ≥ 500 μm (P≤0.011). Not all cRORA lesions show a difference in the number of deep visual sensitivity defects compared with iRORA. Instead, hypertransmission ≥ 500 μm, complete RPE loss ≥ 250 μm, and nGA ≥ 500 μm are all OCT features independently associated with deep visual sensitivity detects that could help inform the definition of end-stage atrophy on OCT imaging. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

OPA1 Dominant Optic Atrophy: Pathogenesis and Therapeutic Targets.

OPA1 Dominant Optic Atrophy: Pathogenesis and Therapeutic Targets.

Minimum Ganglion Cell Layer Thickness is the Best Structural Predictor of Visual Function in Leber Hereditary Optic Neuropathy

Background: Patients with Leber hereditary optic neuropathy, a genetic cause of severe optic atrophy and blindness, demonstrate characteristic structural changes measurable through optical coherence tomography, including initial swelling of the retinal nerve fiber layer and progressive thinning of the ganglion cell layer. After symptomatic conversion, patients experience progressive vision loss, often with dense central scotomas. Aims: This study aims to explore the predictive potential of ocular structural measurements to visual function in patients with Leber hereditary optic neuropathy. Methods: Medical records were reviewed retrospectively for patients with Leber hereditary optic neuropathy clinical testing. Structural measurements, including the average thickness of the ganglion cell layer, the retinal nerve fiber layer, and minimum thickness of the ganglion cell layer, measured through optical coherence tomography were obtained along with measures of visual function such as visual acuity and mean deviation of visual field testing. Simple and multivariable linear regressions were performed to determine correlations between structural measurements and visual functions. Analyses were conducted for all patients, and subgroup of symptomatic patients. Results: Overall, 92 eyes were included with 78 symptomatic eyes. Across all patients, the minimum ganglion cell layer thickness had the highest correlation coefficient with visual acuity (Beta -0.632, adjusted R2 0.396) and with visual field function (Beta 0.572, adj. R2 0.320) compared to the average thickness of the ganglion cell layer (Beta 0.474, adj. R2 0.216) and retinal nerve fiber layer (Beta 0.481, adj. R2 0.223). In multivariate analysis, the minimum ganglion cell layer thickness was the only significant measurement that correlated with visual acuity across all eyes (Beta -0.527, P&lt;0.001) and symptomatic eyes (Beta -0.479, P&lt;0.001). The minimum ganglion cell layer thickness (Beta 0.440, P&lt;0.001) and retinal nerve fiber layer average thickness (0.258, P=0.023) were significant structural measurements correlating to visual field function. Conclusion: The minimum ganglion cell layer thickness is the best structural measure predictor for visual field and visual acuity compared to other common structural measurements in patients with Leber hereditary optic neuropathy. It is a good predictor even when evaluating only symptomatic eyes. Additional attention toward the minimum ganglion cell layer thickness may offer further insight into a patient’s visual potential and the natural history of this disease.

Optic Flow Processing in Patients With Macular Degeneration.

Optic flow processing was characterized in patients with macular degeneration (MD). Twelve patients with dense bilateral scotomas and 12 age- and gender-matched control participants performed psychophysical experiments. Stimuli were dynamic random-dot kinematograms projected on a large screen. For each component of optic flow (translational, radial, and rotational), we estimated motion coherence discrimination thresholds in our participants using an adaptive Bayesian procedure. Thresholds for translational, rotational, and radial patterns were comparable between patients and their matched control participants. A negative correlation was observed in patients between the time since MD diagnosis and coherence thresholds for translational patterns. Our results suggest that in patients with MD, selectivity to optic flow patterns is preserved.

Visual Motion Coherence Responses in Human Visual Cortex.

Random dot kinematograms (RDKs) have recently been used to train subjects with cortical scotomas to perform direction of motion discrimination, partially restoring visual motion perception. To study the recovery of visual perception, it is important to understand how visual areas in normal subjects and subjects with cortical scotomas respond to RDK stimuli. Studies in normal subjects have shown that blood oxygen level-dependent (BOLD) responses in human area hV5/MT+ increase monotonically with coherence, in general agreement with electrophysiology studies in primates. However, RDK responses in prior studies were obtained while the subject was performing fixation, not a motion discrimination condition. Furthermore, BOLD responses were gauged against a baseline condition of uniform illumination or static dots, potentially decreasing the specificity of responses for the spatial integration of local motion signals (motion coherence). Here, we revisit this question starting from a baseline RDK condition of no coherence, thereby isolating the component of BOLD response due specifically to the spatial integration of local motion signals. In agreement with prior studies, we found that responses in the area hV5/MT+ of healthy subjects were monotonically increasing when subjects fixated without performing a motion discrimination task. In contrast, when subjects were performing an RDK direction of motion discrimination task, responses in the area hV5/MT+ remained flat, changing minimally, if at all, as a function of motion coherence. A similar pattern of responses was seen in the area hV5/MT+ of subjects with dense cortical scotomas performing direction of motion discrimination for RDKs presented inside the scotoma. Passive RDK presentation within the scotoma elicited no significant hV5/MT+ responses. These observations shed further light on how visual cortex responses behave as a function of motion coherence, helping to prepare the ground for future studies using these methods to study visual system recovery after injury.

Benefit of Stimulus Size V Perimetry for Patients With a Dense Central Scotoma From Leber's Hereditary Optic Neuropathy.

PurposeLeber's hereditary optic neuropathy (LHON) is the most common mtDNA optic neuropathy. It most frequently causes dense bilateral central scotomas that are often characterized in clinical studies by Humphrey visual field testing (HVF) using a stimulus size III. This provides numerical quantification of the visual field defect using the mean deviation. However, this size III testing strategy has limitations. We used stimulus size V to monitor these patients and evaluated intertest variability and dynamic range to determine the testing reliability and reproducibility.MethodsThis was a longitudinal retrospective cohort study comparing Stimulus III and Stimulus V HVF of 62 LHON patients who had reached the plateau stage of the disease. The intertest variability and mean defect were calculated for both stimulus sizes for 38 patients. The mean defect for stimulus size V was calculated using an algorithm developed by the University of Iowa Visual Field Reading Center.ResultsStimulus size V HVFs had lower inter-test variability as measured by mean defect standard deviation (Z = 169, P < 0.01). The floor effect seen with Stimulus III HVF in LHON, was less pronounced with Stimulus V HVF. The correlation of stimulus size III and V mean defect was strong (r = 0.90, P < 0.01), and a mathematical model was constructed to calculate the Stimulus size V mean defect from the Stimulus size III results (MDstimV = 0.988 x MDStimIII + 1.35, R2 = 0.82 P < 0.01).ConclusionsStimulus size V HVF had lower intertest variability and a better dynamic range than Stimulus size III HVF in LHON patients. This makes the stimulus V HVF a more reliable metric to follow LHON patients especially in clinical trials. The mathematical model presented can be used to generate a Stimulus V equivalent mean defect from Stimulus III HVFs.Translational RelevanceUsing Stimulus V HVF in LHON patients increases its ability to detect and quantify a response to treatment, making it a useful metric for future LHON clinical trials and the clinical setting.

Nonarteritic Anterior Ischemic Optic Neuropathy Simultaneously Associated with Hashimoto’s Thyroiditis

Purpose To report one case of nonarteritic anterior ischemic optic neuropathy (NAION) simultaneously associated with Hashimoto’s thyroiditis. Case summary A-51-year-old man with no underlying disease and painless blurring of vision in his left eye that lasted for a week visited our office. His best-corrected visual acuity was 20/20 in the right eye and 20/1,000 in the left eye. Ophthalmological examination showed a relative afferent pupillary defect in the left eye. Fundoscopic examination revealed swelling of the left optic disc; however, orbital magnetic resonance imaging was normal. Visual field testing by automated perimetry showed a dense central scotoma defect in the left eye. The possibility of optic neuritis was considered; thus, intravenous methylprednisolone (1 g/day) was initiated for 3 consecutive days. Three days after therapy, his visual field showed an inferior altitudinal defect; thus, anterior ischemic optic neuropathy was diagnosed in the left eye. Before the therapy, the anti-thyroid peroxidase antibody level was high, and Hashimoto thyroiditis was detected by thyroid ultrasonography. Conclusions This is the first reported case of NAION associated with concurrent Hashimoto’s thyroiditis. Notably, the patient had none of the risk factors associated with NAION. Keywords: Autoimmune diseases; Hashimoto’s thyroiditis; Nonarteritic anterior ischemic optic neuropathy; Optic disc swelling

MORPHOFUNCTIONAL EVALUATION OF MACULAR-FOVEAL CAPILLARIES

To analyze the macular function of eyes with macular-foveal capillaries (MFC), a condition characterized by the absence of the foveal avascular zone (FAZ), identified by optical coherence tomography angiography. Eight eyes with MFC at optical coherence tomography angiography and normal visual acuity were consecutively recruited. Eight eyes of healthy subjects were enrolled as healthy controls. All eyes underwent optical coherence tomography, optical coherence tomography angiography, best-correct visual acuity, low-luminance visual acuity, contrast sensitivity measurement, colour vision tests, and both mesopic and scotopic microperimetry. Best-corrected visual acuity, low-luminance visual acuity, contrast sensitivity, and colour vision tests did not differ between the two groups. At mesopic microperimetry, both foveal retinal sensitivity and mean mesopic retinal sensitivity of the central 1° were statistically inferior in MFC versus control eyes (P < 0.0001 and P < 0.0001, respectively). At scotopic microperimetry, a dense foveal scotoma, normally present in control eyes, was completely lacking in MFC eyes. Scotopic foveal retinal sensitivity was statistically superior in MFC versus control eyes (P = 0.009). The absence of the foveal dense scotoma in scotopic conditions underlines that the foveal rod-free zone is not present when capillaries are present in this area. An anomalous foveal distribution of photoreceptors, with both rods and cones present in this area, may be postulated in MFC eyes.

Faster Sensitivity Loss around Dense Scotomas than for Overall Macular Sensitivity in Stargardt Disease: ProgStar Report No. 14

Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS. Multicenter, international, prospective cohort study: ProgStar Study. Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS). Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n= 361), and the eMS was 9.3 ± 3.3 dB (n= 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β=-1.33; P < .001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β= .09; P= .461). In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.

Visual Function at the Atrophic Border in Choroideremia Assessed with Adaptive Optics Microperimetry

Recent advances in retinal imaging allow visualization of structural abnormalities in retinal disease at the cellular level. This study used adaptive optics (AO) microperimetry to assess visual sensitivity with high spatial precision and to examine how function varies across 2 phenotypic features observed in choroideremia: atrophic lesion borders and outer retinal tubulations (ORTs). Cross-sectional study. Twelve choroideremia patients. A custom AO scanning light ophthalmoscope (AOSLO) equipped with both confocal and nonconfocalsplit-detection imaging methods was used to image the photoreceptor inner and outer segment mosaics. For AO microperimetry, circular 550-nm stimuli were presented through the AOSLO system; stimuli were either 9.6 or 38.3 arcmin2 (approximately 60 or 15 times smaller than a Goldman III stimulus). Test locations were identified in structural images and stimuli were targeted to these locations using real-time retinal tracking combined with measurements of transverse chromatic aberration. Psychophysical detection thresholds were measured at the atrophic border in 12 patients. Additionally, visual sensitivity was probed along ORTs in 4patients. Visual sensitivity thresholds measured with AO microperimetry at retinal locations corresponding to structural phenotypes observed on AOSLO retinal images. In choroideremia, sharp borders between intact central islands of the photoreceptor mosaic and complete atrophy of the outer retina and retinal pigment epithelium were observed in both split-detection and confocal structural images. Adaptive optics microperimetry at locations spanning these borders showed a commensurately sharp decrease in function, with readily measurable visual sensitivity on one side and dense scotoma on the other. These functional transitions often occurred over a distance smaller than the diameter of the Goldman III stimulus. Thresholds measured along ORTs showed dense scotoma over the tubule in all 4 participants, despite the visibility of remnant cone inner segments on the AO images. Choroideremia patients exhibited sharp functional transitions that collocated with structural transitions from intact to severely degenerated retina. We found no evidence of visual sensitivity over ORTs. Measuring cone function with high resolution offered insight into disease mechanisms and may enable precise assessment of whether experimental therapies, such as gene therapy, provide a functional benefit.

THUR 149 ANCA/MPO vasculitis presenting with bilateral ischaemic optic neuropathy

An 80 year old gentleman presented with bilateral, sequential ischaemic optic neuropathy. He initially developed progressive loss of vision in left eye with loss of colour vision and subsequently developed similar symptoms in the right eye with headaches, weight loss, malaise and lethargy. His visual acuity dropped to 6/12 on the right and counting fingers on the left. He had a dense central scotoma in left eye with left-sided RAPD but no other focal neurological deficits.Blood tests revealed an ESR of 107 with an MPO ANCA titre of 19. MRI brain with contrast showed prominent meningeal enhancement and infiltration with ischaemic changes in the brain. CSF analysis revealed WCC of 24 (95% lymphocytes), RCC 22 and protein 0.4 g/L with negative bacterial culture. Temporal artery biopsy was normal.He was treated initially with IV methylprednisolone and 6 cycles of IV cyclophosphamide and subsequently put on methotrexate. His systemic symptoms have resolved completely and his visual acuity continues to gradually improve.MPO-ANCA vasculitis can mimic temporal arteritis and should be considered in patients presenting with an ischaemic optic neuropathy. It is also a treatable cause of meningeal disease.

Visual Cortex Activation in Patients With Stargardt Disease.

Primary visual cortex (PVC) contains a retinotopic map in which the central visual field (CVF) is highly magnified compared to the peripheral field. Several studies have used functional magnetic resonance imaging (fMRI) in patients with macular degeneration to assess the reorganization of visual processing in relationship with the development of extrafoveal preferred retinal locus (PRL). We evaluated the functional response in PVC and its correlation with retinal parameters in patients with Stargardt disease due to ABCA4 mutations (STGD1). Twenty-four STGD1 patients underwent best-corrected visual acuity, full-field standard electroretinogram (ERG), optical coherence tomography, and microperimetry. Furthermore, patients underwent fMRI to assess cerebral activation during visual stimulation by a flickering checkerboard in four PVC subdivisions, corresponding to 0° to 5° (V1), 5° to 10° (V2), 10° to 15° (V3), and 15° to 40° (V4) of CVF. Higher ERG responses were significantly (P < 0.0125) associated with larger functional cerebral response in V1, V2, and V3 subdivisions. Moreover, larger retinal pigment epithelium atrophy area was significantly (P < 0.0125) associated with smaller PVC activation in V2 and V3 subdivisions. Larger activation in V1 subdivision was significantly (P = 0.001) associated with higher mean macular sensitivity and smaller dense scotoma size. Finally, our results showed reduced activation in V2 and V3 with increased PRL eccentricity. Our study, for the first time in the literature, showed stronger PVC activation in STGD1 patients with a more preserved retinal function and macular structure. Furthermore, our study data strongly suggest that the evaluation of neuronal reorganization could be performed by considering only retinal parameters, particularly ERG responses.

Intersession Test-Retest Variability of Microperimetry in Type 2 Macular Telangiectasia.

PurposeMicroperimetry is used as an endpoint in type 2 macular telangiectasia (mactel) trials. The change required for defining disease progression depends on measurement error. We determined the threshold of test–retest variability (TRV) of microperimetry in mactel.MethodsA prospective study was done of 24 patients with stable mactel enrolled in a tertiary eye clinic. Each patient underwent three sessions of microperimetry separated by a median of 28 days. An identical testing protocol was used: 4-2 staircase algorithm at 37 loci radial grid covering central 6°. Microperimetry variables were compared across three visits. TRV was quantified by calculating the coefficients of repeatability (CRs) for mean and median foveal sensitivity and the number of loci with dense scotoma (DS) or normal sensitivity (NS). The 95% confidence intervals (CIs) for CRs were calculated.ResultsMean and median foveal sensitivity increased from first to second testing sessions. Test duration, visual acuity, number of loci with DS, and fixation stability remained stable through the three test sessions. The intersession CRs for mean and median foveal sensitivity were 2.6 (95% CI, 1.8–3.3) and 2.4 (95% CI, 1.7–3.1) dB, respectively. CRs for the number of DS and NS loci were 5 and 12 loci. CR for both logBCEA63 and logBCEA95 was 1.0 (95% CI, 0.8–1.2).ConclusionsThe first microperimetry examination should be discarded due to learning effects. TRV in foveal sensitivity may be as high as 3.3 and 3.1 dB (∼0.3 log unit; 2× change) for its mean and median.Translational RelevanceOur results have implications for the design of clinical trials in mactel.

Hemifield Slide Phenomenon from Pituitary Macroadenoma

Purpose: Describe a Case Report. Introduction: Pituitary apoplexy (PA) is a rare endocrine emergency, which can occur due to acute hemorrhage or infarction of pituitary gland, usually in the context of a pituitary macroadenoma. 1 The most frequent ophthalmologic symptoms/sings are impaired visual acuity, visual field defects and diplopia. 2,3 A dense bitemporal hemianopic scotoma can cause a rare nonparetic diplopia, so-called hemifield slide phenomenon. Results and Conclusions: This brief report describes a patient with this phenomenon caused by a PA from a pituitary macroadenoma. 2,3,4

The Photopic Negative Response: An Objective Measure of Retinal Ganglion Cell Function in Patients With Leber's Hereditary Optic Neuropathy.

The photopic negative response (PhNR) is a slow negative component of a flash photopic full-field ERG that has been shown to be specific for retinal ganglion cell (RGC) activity. Direct evaluation of RGC function is desirable in patients with Leber's hereditary optic neuropathy (LHON) in which the loss of central acuity can make it difficult to monitor patients with standard metrics. The purpose of this study was to evaluate the use of PhNR as an objective noninvasive clinical metric in LHON. Full-field photopic ERG recordings were collected in subjects with the mt.11778G>A/ND4 LHON mutation using a red on blue stimulus. The PhNR was identified using a computer-based automated detection system, and data were manually examined to remove movement artifacts. The PhNR amplitude was compared between controls (n = 13), carriers (n = 17), and affected (n = 6). Mean PhNR amplitude decreased significantly across groups (P < 0.0001). Post hoc Tukey's test revealed a significant decrease in PhNR amplitude between carriers and controls (P < 0.05) and between carriers and affected (P < 0.01). We are able to demonstrate that the PhNR amplitude is significantly decreased in patients affected by LHON compared to carriers in a well-described pedigree. Surprisingly, there was also a decrease in PhNR in carriers, suggesting potential subclinical RGC dysfunction in some carriers. This is important in patients affected with LHON who typically have a dense central scotoma. The PhNR may be a useful objective outcome measure for future clinical trials.

Posner Schlossman Syndrome

Thirty-two years old male patient presented with four day history of mild redness, pain and blurring of vision of the left eye. He gave history of similar episode 4-5 months back and it subsided with treatment. Visual acuity on presentation was 6/6 RE and 5/60 → 6/12 with -1.5 DSph/-2.75 D Cyl at 110o (left eye). Anterior segment was normal in the right eye. In the left eye, fine keratic precipitates on cornea and trace anterior chamber cells and flare were noted. Pigments were seen on anterior capsule of lens. Dilated fundus examination revealed a normal appearing disc with no cup in right eye and pale disc with C:D ratio 0.8 with a thin neuro-retinal rim in the left eye. Colour vision was normal. Intraocular pressure (IOP) was 14 and 35 mm Hg by applanation in the right and left eyes, respectively. On gonioscopy ciliary body band was visible for 360 degree without any peripheral anterior synechiae or inflammatory deposits. Automated perimetry revealed full visual field in the right eye and a dense scotoma with central island of field in the left eye. He was treated with oral and topical antiglaucoma medications along with topical steroids. On follow up, his vision was 6/6 (right eye) and 6/12 (left eye) with IOP of 12 and 16 mm Hg.

Probing Human Visual Deficits with Functional Magnetic Resonance Imaging.

Much remains to be understood about visual system malfunction following injury. The resulting deficits range from dense, visual field scotomas to mild dysfunction of visual perception. Despite the predictive value of anatomical localization studies, much patient-to-patient variability remains regarding (a) perceptual abilities following injury and (b) the capacity of individual patients for visual rehabilitation. Visual field perimetry is used to characterize the visual field deficits that result from visual system injury. However, standard perimetry mapping does not always precisely correspond to underlying anatomical or functional deficits. Functional magnetic resonance imaging can be used to probe the function of surviving visual circuits, allowing us to classify better how the pattern of injury relates to residual visual perception. Identifying pathways that are potentially modifiable by training may guide the development of improved strategies for visual rehabilitation. This review discusses primary visual cortex lesions, which cause dense contralateral scotomas.

MAPPING THE DENSE SCOTOMA AND ITS ENLARGEMENT IN STARGARDT DISEASE.

To describe the enlargement of the dense scotoma over time in Stargardt disease and to highlight methodologic issues in tracking enlargement. Retrospective study of patients with full mapping of the border of the dense scotoma using the MP-1 for at least two visits. 14 eyes of 7 patients met this criterion. Patients had median of 3 visits (range 2-5), with median total follow-up of 4.5 years (range 1.5-8). Mean baseline visual acuity was 20/56 (range 20/25-20/200), mean baseline dense scotoma area was 2.23 mm (range 0.41-5.48), and mean dense scotoma enlargement rate was 1.36 mm/year (range 0.22-2.91). The younger patients tended to have more rapid loss of visual acuity, which tended to plateau when the visual acuity was 20/100 or worse. The patients who developed Stargardt before age 20 years, and the single patient who developed Stargardt disease after age 40 years, had more rapid enlargement rates, with preservation of central vision in the oldest patient. The ability to precisely define the dense scotoma area was dependent on the density location of the points tested; this led to significant variability in the assessment of the scotoma enlargement rate in three of the seven patients. The dense scotoma was not described adequately by the extent of the homogeneous dark area on fundus autofluorescence imaging. Microperimetry is necessary for mapping the scotoma in patients with Stargardt disease, because current imaging is not adequate. Standardized grid testing, plus a standardized procedure for refining the border of the dense scotoma, should allow more precise testing and longitudinal assessment of enlargement rates.