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Optical coherence tomography angiography findings of choroidal neovascularization in pseudoxanthoma elasticum

Angioid streaks (AS) are the most common ocular manifestation in patients with pseudoxanthoma elasticum (PXE). The major cause of severe visual loss in patients with AS is choroidal neovascularization (CNV). We report the optical coherence tomography angiography (OCTA) findings of CNV in a patient with PXE and angioid streaks. A 51-year-old man with PXE presented with visual disturbance in his right eye. Best corrected visual acuity was 20/30 OD and 20/30 OS. Funduscopic examination revealed angioid streaks and type 1 NV in his right eye. Multimodal imaging including OCTA demonstrated CNV nasal to the fovea. The morphology and configuration of CNV followed the path of the AS. OCTA combined with other multimodal imaging modalities may be a useful tool for diagnosing CNV secondary to angioid streaks in patients with pseudoxanthoma elasticum. The configuration of CNV in these may follow the path of angioid streaks implicating Bruch’s membrane disruption as an important anatomical change in the pathogenesis of CNV.

Efficacy of Primary Collagen Cross-Linking with Photoactivated Chromophore (PACK-CXL) for the Treatment of Staphylococcus aureus-Induced Corneal Ulcers.

Purpose: To evaluate the efficacy of corneal collagen cross-linking (CXL) with photoactivated riboflavin (PACK-CXL) as primary therapy for Staphylococcus aureus–induced corneal ulcers in a rabbit model. Methods: The right eye of 40 rabbits was inoculated with S. aureus to induce formation of central corneal ulcers (day 1). The ulcer was examined on day 5, and rabbits were randomly assigned to 4 groups—group A: no treatment (control); group B: topical antibiotic treatment (cefazolin 50 mg/mL, garamycin 14 mg/mL drops, chloramphenicol 5% ointment every 2 hours); group C: PACK-CXL; group D: PACK-CXL + topical antibiotics. Follow-up by biomicroscopy was performed on day 5 and then every week for 1 month. The main outcome measures included infiltrates or the scar diameter, time to healing, time to full epithelialization, and a change in corneal thickness. Results: After 1 month of treatment, group C ulcers had the smallest mean scar diameter (8.8 mm2), followed by groups D (11.2 mm2), B (13.0 mm2), and A (24.5 mm2) (P = 0.011). Group C had the shortest mean healing time (15.5 days), followed by groups D (17.2 days), B (19.7 days), and A (21.8 days). Analysis of relative reduction in the infiltrate size from day 5 yielded better results for groups C (P = 0.039) and D (P = 0.034) than those of group B. Conclusions: We demonstrate a beneficial effect of PACK-CXL as primary treatment, either as stand-alone or as an adjuvant to antimicrobial therapy.

Understanding aneurysmal type 1 neovascularization (polypoidal choroidal vasculopathy): a lesson in the taxonomy of ‘expanded spectra’ - a review: Aneurysmal type 1 neovascularization

The term aneurysmal type 1 neovascularization is derived from terminology, which is established in the literature but has fallen out of use. We believe that aneurysmal type 1 neovascularization accurately describes the lesions which define the entity known as polypoidal choroidal vasculopathy (PCV). Over the last three decades, the clinical spectrum of PCV has expanded to recognize the occurrence of the aneurysmal (polypoidal) lesions in different contexts, resulting in a complex and unwieldy taxonomy based sometimes on circumstantial findings rather than mechanistic considerations. Advances in multimodal imaging provides increasingly convincing evidence that the lesions which define various forms of PCV are indeed vascular and arise from type 1 neovascular networks. The understanding of PCV as type 1 neovascularization with aneurysms renews focus on the question as to why some patients with type 1 neovascularization develop aneurysms while others do not. Conceptual themes and potential for further study are discussed.

Efficacy of Subconjunctival Aflibercept Versus Bevacizumab for Prevention of Corneal Neovascularization in a Rat Model.

Purpose: We aimed to evaluate the efficacy of subconjunctival aflibercept, a vascular endothelial growth factor trap compound, for the treatment of corneal neovascularization in a rat model. Methods: Chemical burn was produced in the central cornea of 31 male Sprague–Dawley rats. Animals were randomized to receive treatment with subconjunctival injection of 0.08 mL aflibercept (25 mg/mL), 0.05 mL bevacizumab (25 mg/mL), or 0.05 mL physiologic saline. Corneal neovascularization was evaluated on postinjury days 1, 3, 7, 9, and 13 by corneal photographs. The rats were killed on day 21 and samples were collected for histological and flat-mount immunofluorescence analyses. Results: In all rats, vascular sprouting began on day 3, reached maximum density on days 7–9, and spontaneously regressed thereafter. Mean burn area in the central cornea comprised ∼15% of the total corneal area. The aflibercept group had a significantly smaller relative area of neovascularization than both control group (P < 0.05, 12.27 ± 9.91, 29.66 ± 9.96 days 7) and bevacizumab group (P < 0.05, 12.27 ± 9.91, 21.27 ± 8.19 days 7 and 15.5 ± 10.25, 32.38 ± 9.44 days 9; Mann–Whitney test). On histological study, hematoxylin and eosin staining revealed blood vessels extending to the central cornea in the control and bevacizumab groups and limited to the periphery in the aflibercept group. Immunofluorescence study with an endothelial marker revealed a smaller area of staining in the aflibercept group. Conclusions: Aflibercept effectively inhibits corneal neovascularization in a rat model of chemical burn–induced neovascularization and warrants further study for potential use in humans.

Scleral Cross-linking Using Riboflavin and Ultraviolet-A Radiation for Prevention of Axial Myopia in a Rabbit Model

Myopic individuals, especially those with severe myopia, are at higher-than-normal risk of cataract, glaucoma, retinal detachment and chorioretinal abnormalities. In addition, pathological myopia is a common irreversible cause of visual impairment and blindness. Our study demonstrates the effect of scleral crosslinking using riboflavin and ultraviolet-A radiation on the development of axial myopia in a rabbit model. The axial length of the eyeball was measured by A-scan ultrasound in New Zealand white rabbits aged 13 days (male and female). The eye then underwent 360° conjunctival peritomy with scleral crosslinking, followed by tarsorrhaphy. Axial elongation was induced in 13 day-old New Zealand rabbits by suturing their right eye eyelids (tarsorrhaphy). The eyes were divided into quadrants, and every quadrant had two scleral irradiation zones, each with an area of 0.2 cm² and a radius of 4 mm. Crosslinking was performed by dropping 0.1% dextran-free riboflavin-5-phosphate onto the irradiation zones 20 sec before ultraviolet-A irradiation and every 20 sec during the 200 sec irradiation time. UVA radiation (370 nm) was applied perpendicular to the sclera at 57 mW/cm² (total UVA light dose, 57 J/cm²). Tarsorrhaphies were removed on day 55, followed by repeated axial length measurements. This study demonstrates that scleral crosslinking with riboflavin and ultraviolet-A radiation effectively prevents occlusion-induced axial elongation in a rabbit model.

Choroidal Thickness Influences Near-Infrared Reflectance Intensity in Eyes With Geographic Atrophy Due To Age-Related Macular Degeneration

Purpose To evaluate the effects of retinal and choroidal thickness on near-infrared reflectance (NIR) scanning laser ophthalmoscopy in eyes with geographic atrophy (GA) secondary to non-neovascular age-related macular degeneration (AMD). Methods This was a cross-sectional review of the clinical records and multimodal imaging data of eyes diagnosed with GA secondary to non-neovascular AMD. Imaging modalities included color fundus photography, fundus autofluorescence, NIR, and structural spectral-domain optical coherence tomography (SD-OCT). On SD-OCT images, the foveal retina thickness and the subfoveal choroidal thickness were measured by two independent readers. Near-infrared reflectance intensity within areas of GA was subjectively graded as hyperreflective, isoreflective, or hyporeflective and objectively estimated by using ImageJ to calculate the mean gray scale value within each GA area. A linear regression analysis was performed to model the relationship between mean NIR gray scale value and retinal and choroidal thickness. Results One hundred four eyes of 104 patients with a mean age of 81.3 years (SD: ±8.3) were included. The area of GA was hyperreflective on NIR in 88 eyes (85%), isoreflective in 13 eyes (12%), and hyporeflective in 3 eyes (3%). The mean foveal retinal thickness was 101.5 μm (SD: ±54) showing no significant relationship with mean NIR (P = 0.464); and the mean subfoveal choroidal thickness was 172.6 μm (SD: ±114.7) showing a statistically significant relationship with mean NIR intensity in the linear regression analysis (r = 0.590; r2 = 0.348; P < 0.00001). Conclusions Variations in choroidal thickness appear to influence NIR intensity in areas of GA and have the potential to affect image interpretation. The recognition of this relationship may provide useful information regarding choroidal thickness.

Role of Concomitant Triamcinolone Acetonide Injection in Small-Gauge Vitrectomy for Idiopathic Epiretinal Membrane Peel.

PurposeThe concomitant use of triamcinolone acetonide (TA) at the completion of pars plana vitrectomy for the treatment of epiretinal membrane may speed up the anatomical and functional outcomes of surgery. We report the outcome of patients undergoing small-gauge vitrectomy for idiopathic epiretinal membrane peel with or without adjuvant TA therapy. DesignThis is a retrospective, single-center case series. MethodsWe included 75 eyes of 75 individual patients. Twenty-six patients (group A) had an adjuvant TA injection during surgery, whereas 49 patients (group B) were not injected. We assessed the patients for change in visual acuity (VA) and central macular thickness before and after surgery. ResultsGroup A had a mean logarithm of the minimum angle of resolution VA of 0.63 ± 0.33 and 0.51 ± 0.31 preoperatively and 3 months after surgery, respectively. Group B had a mean logarithm of the minimum angle of resolution VA of 0.47 ± 0.17 and 0.36 ± 0.17 preoperatively and 3 months after surgery, respectively. No significant difference was found between the groups in change of VA. The mean central macular thickness for groups A and B patients before surgery was 474.12 ± 120 &mgr;m and 445 ± 85 &mgr;m, decreasing to 369 ± 70 &mgr;m and 386 ± 60 &mgr;m at the final visit, respectively. The difference in macular thickness reduction between the groups was statistically significant. ConclusionsAnatomical and functional improvement was found in both groups after surgery. Macular thickness was further reduced in the group of patients treated with adjuvant TA.

Spontaneous Rupture and Involution of a “Macro–Microaneurysm” in Diabetic Retinopathy

Unusually large microaneurysms (MAs) are a common finding in Coats disease but may also occur in various other retinal vascular disorders including retinal vein occlusion and diabetic retinopathy.1,2 Most very large microaneurysms are found in the peripheral retina, but some may present in the macula where they have been whimsically termed “macro-microaneursyms.” (Personal communication, Lawrence A. Yannuzzi, MD). Herein, we present the multimodal imaging findings of a retinal macro–microaneurysm related to diabetic retinopathy that showed spontaneous involution after rupture. A 73-year-old man was referred for management of diabetic macular edema. Funduscopic examination showed retinal hemorrhages and edema surrounding a single MA in his left eye (Figure 1A). Despite treatment with intravitreal aflibercept (2.0 mg/0.05 mL), the lesion continued to enlarge, reaching a maximal Fig. 1. Multimodal imaging including color photographs (left), en face optical coherence tomography (OCT) angiography of the superficial and deep capillary plexus (middle), and corresponding structural OCT B scans with flow overlay (right) at 15 months (A), 17 months (B), and 20 months (C) after presentation. Red circles (middle) and white arrows (right) indicate the location of the aneurysm. The green and red lines (right) indicate the segmentation boundaries for the corresponding en face OCT angiography. A. Color photograph shows intraretinal hemorrhages and edema surrounding a large microaneurysm with remote lipid exudation. Structural OCT (inset rectangle), corresponding to the red arrow shows the macro– microaneurysm at its maximum diameter of 510 mm. En face OCT angiography and structural OCT with flow overlay show individual capillaries feeding and draining the macro–microaneurysm. There is remodeling of the capillary bed surrounding the lesion with a mild reduction in flow density. There are surrounding cystic spaces within the inner nuclear layer and disruption of the ellipsoid zone beneath the lesion. B. Color fundus photograph shows increased retinal hemorrhage due to spontaneous rupture of the macro–microaneurysm with persistent remote intraretinal lipid. En face OCT angiography and structural OCT with flow overlay show near absence of flow within the lesion that could be real or partly related to shadowing from the hyperreflective intraretinal hemorrhage surrounding the lesion. The intraretinal cysts have resolved. There appears to be persistent flow in single capillary traversing the involved area. C. Color fundus photograph shows involution of the aneurysm with reduced hemorrhage and lipid. En face OCT angiography and structural OCT with flow overlay show resolution of intraretinal hemorrhage and involution of the aneurysm which appears devoid of flow. There is persistent disruption of the ellipsoid zone beneath the lesion.

Retinal Penetration of Intravitreally Injected Tissue Plasminogen Activator: A Rat Model Study

Purpose: To determine whether intravitreal unconjugated tissue plasminogen activator (tPA) (alteplase) can penetrate the intact neural retina and reach the subretinal space in an experimental model. Methods: This study was performed in 24 Sprague-Dawley rats aged 12 weeks. Under general anesthesia, the right eye was injected with either 0.75 μg of 3 μL tPA (14 rats; study group) or saline (10 rats, control group) into the vitreous. Animals were euthanized at 3, 24, and 48 h. The eyes were enucleated, and cryosections were prepared for immunofluorescence staining. Goat anti-tPA antibody was used to detect tPA. Results: In the study group, staining for tPA was detected in the deep retinal layers in all eyes. The staining was deeper and more intense at 3 and 24 h than at 48 h. There was no tPA staining in the retina of eyes injected with saline. Conclusions: This experimental study shows that unconjugated tPA administered into the vitreous is capable of penetrating the deep retinal layers and the subretinal space. These findings suggest that further clinical research is warranted on the benefits of intravitreal tPA in the treatment of submacular hemorrhage.

Macular Atrophy Development and Subretinal Drusenoid Deposits in Anti-Vascular Endothelial Growth Factor Treated Age-Related Macular Degeneration

Purpose To explore the association between presence of subretinal drusenoid deposits (SDD) at baseline in eyes with neovascular age-related macular degeneration (nAMD) with the development of macular atrophy (MA) during anti-vascular endothelial growth factor (VEGF) therapy. Methods There were 74 eyes without pre-existing MA receiving anti-VEGF therapy for nAMD for 2 years or longer analyzed. At least two image modalities that included spectral-domain optical coherence tomography, near-infrared reflectance, fluorescein angiography, and color fundus photos were used to assess for SDD presence, phenotype (dot and ribbon), and location, neovascularization type, and MA. Logistic regression models using generalized estimating equations assessed the association between SDD and the development of MA adjusting for age, neovascularization type, and choroidal thickness. Results SDD were present in 46 eyes (63%) at baseline. MA developed in 38 eyes (51%) during the mean of 4.7 ± 1.2 years of follow-up. Compared with eyes without SDD, those with SDD at baseline were 3.0 times (95% confidence interval [CI] 1.1–8.5, P = 0.0343) more likely to develop MA. Eyes with SDD present in the inferior macula and inferior extramacular fields at baseline were 3.0 times and 6.5 times more likely to develop MA at follow-up than eyes without SDD in these locations (95% CI 1.0–8.9, P = 0.0461 and 95% CI 1.3–32.4, P = 0.0218, respectively). MA development was not associated with a specific SDD phenotype. Conclusions MA frequently developed in eyes during anti-VEGF treatment. SDD were independently associated with MA development. The extension of SDD into the inferior fundus, particularly in the inferior extramacular field, conferred higher odds of subsequent MA development.