Victor E. Malinovsky

In vivo adaptive optics microvascular imaging in diabetic patients without clinically severe diabetic retinopathy

We used a confocal adaptive optics scanning laser ophthalmoscope (AOSLO) to image the retina of subjects with non-proliferative diabetic retinopathy (NPDR). To improve visualization of different retinal features, the size and alignment of the confocal aperture were varied. The inner retinal layers contained clearly visualized retinal vessels. In diabetic subjects there was extensive capillary remodeling despite the subjects having only mild or moderate NPDR. Details of the retinal microvasculature were readily imaged with a larger confocal aperture. Hard exudates were observed with the AOSLO in all imaging modes. Photoreceptor layer images showed regions of bright cones and dark areas, corresponding in location to overlying vascular abnormalities and retinal edema. Clinically undetected intraretinal vessel remodeling and varying blood flow patterns were found. Perifoveal capillary diameters were larger in the diabetic subjects (p<0.01), and small arteriolar walls were thickened, based on wall to lumen measurements (p<.05). The results suggest that existing clinical classifications based on lower magnification clinical assessment may not adequately measure key vascular differences among individuals with NPDR.

Proton therapy for exudative age-related macular degeneration: a randomized, sham-controlled clinical trial☆

PURPOSE To examine the effect of proton beam irradiation on subfoveal choroidal neovascular membranes (CNVM) associated with age-related macular degeneration (AMD).Randomized, prospective, sham-controlled, double-masked treatment trial. METHODS Thirty-seven subjects with subfoveal CNVM due to AMD were randomly assigned to 16-Gy proton irradiation delivered in two fractions 24 hours apart or to sham control treatment. Recruitment was halted at 37 subjects for ethical reasons regarding randomization to sham treatment when Food and Drug Administration approval of Visudyne was anticipated. RESULTS Proton irradiation was associated with a trend toward stabilization of visual acuity, but this association did not reach statistical significance. No correlations were found within the fluorescein angiography data, including greatest linear dimension of CNVM total size, area of active leakage, area of associated subretinal hemorrhage, and intensity. CONCLUSIONS With the acceptance of photodynamic therapy, future studies will require more complex design and larger sample size to determine whether radiation can play either a primary or adjunctive role in treating these lesions.

Regulation of intraocular pressure after water drinking

PURPOSE Acute oral water loading transiently elevates intraocular pressure (IOP) via mechanisms that remain unexplained. We tested the possibilities that water drinking might elevate IOP by creating a blood-aqueous osmotic gradient, or that it might instead alter active ion pumping and the formation of aqueous humor. METHODS In the first series, 16 young, healthy individuals were studied during dehydration and for 1 hour after rehydration (14 mL H2O/kg body weight). Hematocrit, total plasma osmolality, and plasma colloid osmotic pressure were determined simultaneously with measurements of IOP. In a second series (N = 16), rehydration occurred after pretreatment with either placebo or a topical carbonic anhydrase inhibitor (1 drop 2% dorzolamide in each eye, 12 and 2 hours before oral water loading). RESULTS In both series, mean IOP increased significantly 15 minutes after water ingestion and remained elevated above baseline for 45 minutes. In contrast, colloid osmotic pressure and hematocrit were unaltered by water drinking, and neither these variables nor total plasma osmolality correlated with IOP. In the second series, pretreatment with dorzolamide reduced baseline IOP, but failed to alter the magnitude or time course of IOP elevations induced by water drinking. CONCLUSION Because water drinking failed to create a blood-ocular osmotic pressure gradient, neither vitreous hydration nor increased aqueous ultrafiltration can explain increases in IOP after acute hydration. Because the increase in ocular tension apparently also is independent of active bicarbonate pumping, factors affecting aqueous drainage must explain the water drinking effect.

Contrast Sensitivity Perimetry and Clinical Measures of Glaucomatous Damage

Purpose To compare conventional structural and functional measures of glaucomatous damage with a new functional measure—contrast sensitivity perimetry (CSP-2). Methods One eye each was tested for 51 patients with glaucoma and 62 age-similar control subjects using CSP-2, size III 24-2 conventional automated perimetry (CAP), 24-2 frequency-doubling perimetry (FDP), and retinal nerve fiber layer (RNFL) thickness. For superior temporal (ST) and inferior temporal (IT) optic disc sectors, defect depth was computed as amount below mean normal, in log units. Bland-Altman analysis was used to assess agreement on defect depth, using limits of agreement and three indices: intercept, slope, and mean difference. A criterion of p < 0.0014 for significance used Bonferroni correction. Results Contrast sensitivity perimetry-2 and FDP were in agreement for both sectors. Normal variability was lower for CSP-2 than for CAP and FDP (F > 1.69, p < 0.02), and Bland-Altman limits of agreement for patient data were consistent with variability of control subjects (mean difference, −0.01 log units; SD, 0.11 log units). Intercepts for IT indicated that CSP-2 and FDP were below mean normal when CAP was at mean normal (t > 4, p < 0.0005). Slopes indicated that, as sector damage became more severe, CAP defects for IT and ST deepened more rapidly than CSP-2 defects (t > 4.3, p < 0.0005) and RNFL defects for ST deepened more slowly than for CSP, FDP, and CAP. Mean differences indicated that FDP defects for ST and IT were on average deeper than RNFL defects, as were CSP-2 defects for ST (t > 4.9, p < 0.0001). Conclusions Contrast sensitivity perimetry-2 and FDP defects were deeper than CAP defects in optic disc sectors with mild damage and revealed greater residual function in sectors with severe damage. The discordance between different measures of glaucomatous damage can be accounted for by variability in people free of disease.

Imaging Glaucomatous Damage Across the Temporal Raphe.

PURPOSE To image and analyze anatomical differences at the temporal raphe between normal and glaucomatous eyes using adaptive optics scanning laser ophthalmoscopy (AOSLO) and optical coherence tomography (OCT), and to relate these differences to visual field measurements. METHODS Nine glaucomatous eyes of 9 patients (age 54-78 years, mean deviation of visual field [MD] -5.03 to -0.20 dB) and 10 normal eyes of 10 controls (age 54-81, MD -1.13 to +1.39 dB) were enrolled. All the participants were imaged in a region that was centered approximately 9° temporal to the fovea. The size of imaging region was at least 10° vertically by 4° horizontally. The raphe gap, defined as the distance between the superior and inferior retinal nerve fiber layer (RNFL) bundles, was measured. A bundle index was computed to quantify the relative reflectivity and density of the nerve fiber bundles. We also measured thickness of the ganglion cell complex (GCC) and RNFL. RESULTS The raphe gap was larger in glaucomatous eyes than control eyes. Specifically, eight glaucomatous eyes with local averaged field loss no worse than -3.5 dB had larger raphe gaps than all control eyes. The bundle index, GCC thickness, and RNFL thickness were on average reduced in glaucomatous eyes, with the first two showing statistically significant differences between the two groups. CONCLUSIONS Structural changes in the temporal raphe were observed and quantified even when local functional loss was mild. These techniques open the possibility of using the raphe as a site for glaucoma research and clinical assessment.

Management of neurotrophic keratopathy.

Neurotrophic keratopathy is an epithelial defect associated with fifth nerve damage, arising from numerous etiologies, which can be difficult to treat. Depending on the location of these defects, they can also prove to be sight threatening if treatment is unsuccessful. Several treatment options are available to assist in the resolution of these defects and, due to the serious potential consequences for sight if not well managed, all treatment options should be considered. This reporting of a patient that developed neurotrophic keratopathy after an intraocular surgical procedure includes details of the early, mid and late stages of the epithelial defect, the treatments that were instituted and the outcomes. The various treatments that are available for management of neurotrophic keratopathy and other persistent epithelial defects are discussed.

Individual differences in the shape of the nasal visual field.

Graphical abstract Figure. No Caption available. HighlightsThe stimulus was resistant to peripheral defocus and reduced illumination.Between‐subject differences in the shape of the nasal visual field were substantial.In some people there was no peripheral depression of sensitivity, in most the depression was mild.A few had more severe peripheral depression that persisted in longitudinal testing. ABSTRACT Between‐subject differences in the shape of the nasal visual field were assessed for 103 volunteers 21–85 years of age and free of visual disorder. Perimetry was conducted with a stimulus for which contrast sensitivity is minimally affected by peripheral defocus and decreased retinal illumination. One eye each was tested for 103 volunteers free of eye disease in a multi‐center prospective longitudinal study. A peripheral deviation index was computed as the difference in log contrast sensitivity at outer (25–29° nasal) and inner (8° from fixation) locations. Values for this index ranged from 0.01 (outer sensitivity slightly greater than inner sensitivity) to −0.7 log unit (outer sensitivity much lower than inner sensitivity). Mean sensitivity for the inner locations was independent of the deviation index (R2 < 1%), while mean sensitivity for the outer locations was not (R2 = 38%, p < 0.0005). Age was only modestly related to the index, with a decline by 0.017 log unit per decade (R2 = 10%). Test‐retest data for 21 volunteers who completed 7–10 visits yielded standard deviations for the index from 0.04 to 0.17 log unit, with a mean of 0.09 log unit. Between‐subject differences in peripheral deviation persisted over two years of longitudinal testing. Peripheral deviation indices were correlated with indices for three other perimetric stimuli used in a subset of 24 volunteers (R2 from 20% to 49%). Between‐subject variability in shape of the visual field raises concerns about current clinical visual field indices, and further studies are needed to develop improved indices.

Between-subject variability in asymmetry analysis of macular thickness.

Purpose To investigate the use of asymmetry analysis to reduce between-subject variability of macular thickness measurements using spectral domain optical coherence tomography. Methods Sixty-three volunteers (33 young subjects [aged 21 to 35 years] and 30 older subjects [aged 45 to 85 years]) free of eye disease were recruited. Macular images were gathered with the Spectralis optical coherence tomography. An overlay 24- by 24-degree grid was divided into five zones per hemifield, and asymmetry analysis was computed as the difference between superior and inferior zone thicknesses. We hypothesized that the lowest variation and the highest density of ganglion cells will be found approximately 3 to 6 degrees from the foveola, corresponding to zones 1 and 2. For each zone and age group, between-subject SDs were compared for retinal thickness versus asymmetry analysis using an F test. To account for repeated comparisons, p < 0.0125 was required for statistical significance. Axial length and corneal curvature were measured with an IOLMaster. Results For OD, asymmetry analysis reduced between-subject variability in zones 1 and 2 in both groups (F > 3.2, p < 0.001). Standard deviation for zone 1 dropped from 12.0 to 3.0 &mgr;m in the young group and from 11.7 to 2.6 &mgr;m in the older group. Standard deviation for zone 2 dropped from 13.6 to 5.3 &mgr;m in the young group and from 11.1 to 5.8 &mgr;m in the older group. Combining all subjects, neither retinal thickness nor asymmetry analysis showed a strong correlation with axial length or corneal curvature (R2 < 0.01). Analysis for OS yielded the same pattern of results, as did asymmetry analyses between eyes (F > 3.8, p < 0.0001). Conclusions Asymmetry analysis reduced between-subject variability in zones 1 and 2. Combining the five zones together produced a higher between-subject variation of the retinal thickness asymmetry analysis; thus, we encourage clinicians to be cautious when interpreting the asymmetry analysis printouts.

Foveal localization in non-exudative AMD using scanning laser polarimetry.

Purpose. To determine whether custom scanning laser polarimetry (SLP) images, differing in polarization content, can be used to accurately localize the fovea in the presence of non-exudative age-related macular degeneration (AMD). To determine whether alterations to the foveal structure in non-exudative AMD significantly disrupts the birefringent Henle fiber layer, responsible for the macular cross pattern in some SLP images. To determine whether phase retardation information, specifically color-coded information representing its magnitude and axis, allow better foveal localization than images including retardation amplitude only. Methods. SLP images were acquired in 25 AMD subjects and 25 age-matched controls. Raw data were used to generate five custom image types differing in polarization content. The foveal location was marked by three graders in each image type for each subject. The difference in variability was compared between the AMD subjects and matched controls. We further determined whether the orientation of Henle fiber layer phase retardation improved localization in 10 subjects with the highest variability in images including only phase retardation amplitude. Results. Images that differed in polarization content led to strikingly different visualizations of AMD pathology. The Henle fiber layer remained sufficiently intact to assist in fovea localization in all subjects but with more variability in the AMD group. For both the AMD and matched control group, images containing birefringence amplitude and orientation information reduced the amount of intragrader, intergrader, and interimage variability for estimating foveal location. Conclusions. The disruption in Henle fiber birefringence was evident in the eyes with AMD but nevertheless was sufficient to help in foveal localization despite macular pathology. Phase retardation amplitude and axis of orientation can be a useful tool in foveal localization in patients with AMD.

Diagnosis and management of temporal arteritis : a review and case report

Temporal arteritis is an insidious disease which, if not recognized and treated with high-dosage oral prednisone or intravenous prednisolone, can result in unilateral or even total blindness due to anterior ischemic optic neuropathy (AION) or closure of the central artery of the retina. Unfortunately, the symptoms and clinical signs of temporal arteritis mimic those of a number of other conditions including angle-closure glaucoma, hypertension, migraine, trigeminal neuralgia, temporomandibular joint syndrome, carotid artery occlusive disease, Foster-Kennedy syndrome, and nonarteritic AION. When a patient complains of a severe pain in the temporal region, along with scalp tenderness and a feeling of malaise or depression--with or without episodes of transient loss of vision--he or she should be referred for a diagnostic work-up which includes an erythrocyte sedimentation rate and a temporal artery biopsy. We present here a review of the recent literature concerning temporal arteritis, followed by a report of an unusual case in which high-dosage prednisone therapy was effective in relieving the patients symptoms and lowering the sedimentation rate in spite of a negative temporal artery biopsy.