Sandrine A. Zweifel

Reticular pseudodrusen are subretinal drusenoid deposits.

PURPOSE To characterize reticular pseudodrusen, a potential risk factor for late age-related macular degeneration. DESIGN Retrospective, observational case series. PARTICIPANTS Fifty-eight eyes of 33 patients with pseudodrusen (20 female). METHODS Consecutive patients with reticular pseudodrusen, diagnosed by their typical appearance and distribution using ophthalmoscopy, the blue channel of color fundus photographs, and near infrared images. The patients were imaged by spectral domain optical coherence tomography (SD OCT), and correlations were made between the near infrared images and the SD OCT images. The SD OCT findings in patients with pseudodrusen were compared with previously reported histologic findings of subretinal drusenoid deposits. The histologic specimens were reevaluated with the additional knowledge of the clinical information. MAIN OUTCOME MEASURES Spectral domain optical coherence tomography and histologic characteristics of pseudodrusen. RESULTS The mean age of the 33 patients was 81.7 years. The correlating SD OCT scans showed collections of granular hyperreflective material above the retinal pigment epithelium (RPE), in the subretinal space located primarily between the RPE and the boundary between the inner and outer segments of the photoreceptors (IS/OS boundary). In a more advanced stage, this material formed small mounds that broke through the IS/OS boundary. There were no correlates to the deposits seen under the RPE or in the choroid. These findings were similar in character to previously reported histologic characterization of subretinal drusenoid deposits, which had identified the presence of membranous debris, unesterified cholesterol, and complement within the deposits. CONCLUSIONS Pseudodrusen seen by clinical examination may be subretinal drusenoid deposits seen by histologic examination. This unexpected location suggests that potential pathophysiologic mechanisms on both sides of the RPE need to be taken into account in theories related to the development of age-related macular degeneration.

Prevalence and Significance of Subretinal Drusenoid Deposits (Reticular Pseudodrusen) in Age-Related Macular Degeneration

PURPOSE To determine the prevalence and significance of subretinal drusenoid deposits (reticular pseudodrusen) among patients with age-related macular degeneration (AMD). DESIGN A prospective study with a nested case-control study of consecutive patients with AMD seen in a referral retinal practice. PARTICIPANTS There were 153 patients with AMD, 131 of whom had > or =1 eye with late AMD, which was defined as either central geographic atrophy or choroidal neovascularization. The control group consisted of 101 patients who did not have AMD as their primary diagnosis, central serous chorioretinopathy, high myopia, retinal detachment, or laser treatment in the macular area. METHODS The presence of subretinal drusenoid deposits was determined by 2 methods, using the blue channel of color fundus photograph and the spectral domain optical coherence tomography (SD-OCT) sections. Soft drusen were determined from color fundus photographs and confirmed by SD-OCT. MAIN OUTCOME MEASURES Prevalence of ocular risk factors and subretinal drusenoid deposits in eyes with AMD and their association with late AMD. RESULTS There were 153 patients who had any form of AMD, with a mean age of 80.3 years. Subretinal drusenoid deposits were diagnosed in the case group in 13 (8.7%) of right and 18 (12.0%) of left eyes using the blue channel of the color photograph and in 58 (38.4%) of right and 54 (35.8%) of left eyes using SD-OCT. Soft drusen and subretinal drusenoid deposits detected by SD-OCT were found to be independently correlated with late AMD (soft drusen odds ratio = 16.66 [P<0.001]; subretinal drusenoid deposits as detected by OCT odds ratio = 2.64 [P = 0.034]). In the control group, subretinal drusenoid deposits were diagnosed in 6 (6.5%) of right and 6 (6.3%) of left eyes using SD-OCT. CONCLUSIONS Both soft drusen and subretinal drusenoid deposits occur in patients with AMD and both are significantly associated with late AMD. These findings suggest that detection and classification of drusen and consequently assignment of risk should be based on a methodology that includes SD-OCT.

Do we need a new classification for choroidal neovascularization in age-related macular degeneration?

The introduction of intravitreal antivascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (AMD) has not only improved the quality of life for our patients but also raised the bar for what we consider effective treatment for this disease.1,2 Fortunately,

Outer Retinal Tubulation: A Novel Optical Coherence Tomography Finding

OBJECTIVE To describe tubular structures found in the outer retina seen in a variety of retinal disorders. METHODS Sixty-nine eyes of 63 patients were examined with spectral-domain optical coherence tomography. Optical coherence tomography C-scans were correlated with their corresponding B-scans. The prevalence, number, size, and shape of the tubular structures were determined. RESULTS Branching tubules were identified in the outer retina of 54 patients with age-related macular degeneration and in 9 patients with other diagnoses. The tubules appeared as round or ovoid hyporeflective spaces with hyperreflective borders on the B-scans, measuring 40 to 140 microm high and 40 to 2260 microm wide. Morphologic features ranged from single straight or branching tubules to complex cavitary networks, usually overlying areas of pigment epithelial alteration or subretinal fibrosis. The tubules generally remained stable over time. In a retinal practice specializing in advanced age-related macular degeneration, these structures were identified in 60 of 248 patients (24.2%) seen during a 3-month period. CONCLUSIONS Degenerating photoreceptors may become arranged in a circular or ovoid fashion during a process we propose to term outer retinal tubulation. These changes are apparently common in advanced diseases affecting the outer retina and retinal pigment epithelium. This observation has practical implications because these findings can be misinterpreted as intraretinal or subretinal fluid, possibly prompting unnecessary interventions.

Treat and extend dosing of intravitreal antivascular endothelial growth factor therapy for type 3 neovascularization/retinal angiomatous proliferation.

Purpose: The purpose of this study was to analyze long-term outcomes for the treatment of type 3 neovascularization/retinal angiomatous proliferation using a “Treat and Extend” dosing regimen for antivascular endothelial growth factor therapy. Methods: This was a retrospective analysis of visual acuity and optical coherence tomography data of 11 eyes of 10 consecutive patients with newly diagnosed type 3 neovascularization/retinal angiomatous proliferation treated with intravitreal bevacizumab and/or ranibizumab with at least a 12-month follow-up. Three monthly injections were followed by continued treatment at intervals increasing by 2 weeks per visit, to a maximum of 10 weeks, unless clinical or optical coherence tomography evidence of persistent or recurrent fluid was present, in which case, the interval was shortened. Results: Mean baseline Snellen visual acuity was 20/80, improved to 20/40 at 1 month, and was maintained throughout the 36-month period (n = 11 at 12 months, n = 10 at 24 months, and n = 8 at 36 months) (P < 0.04, paired t-test). The mean center point optical coherence tomography thickness decreased from 320 &mgr;m to 180–230 &mgr;m, and was maintained during the study period (P < 0.02). The mean number of injections was seven in the first year, six in the second year, and seven in the third year. Conclusion: “Treat and Extend” antivascular endothelial growth factor dosing in type 3 neovascularization/retinal angiomatous proliferation delivers promising outcomes at a reduced burden for the patient and health care system compared with monthly and optical coherence tomography-guided dosing regimens.

Enhanced Depth Imaging Optical Coherence Tomography of the Sclera in Dome-Shaped Macula

PURPOSE To examine the posterior anatomic structure of eyes with dome-shaped macula using enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT). DESIGN Retrospective observational case series. METHODS Patients with dome-shaped macula, a condition defined as convex elevation of the macula as compared with the surrounding staphylomatous region in a highly myopic eye, were identified through routine examinations using optical coherence tomography (OCT). EDI-OCT was used to examine their posterior anatomic changes. The scleral thickness was measured from the outer border of the choroid to the outer scleral border under the fovea and 3000 μm temporal to the fovea. RESULTS The mean age of the 15 patients (23 eyes) was 59.3 (± 12.2) years, and the mean refractive error was -13.6 (± 5.0) diopters. The best-corrected visual acuity ranged from 20/15 to 20/800 (median: 20/30). Eight patients (53%) had dome-shaped macula bilaterally. The mean subfoveal scleral thickness in 23 eyes with dome-shaped macula was 570 (± 221) μm, and that in 25 eyes of 15 myopic patients with staphyloma but without dome-shaped macula was 281 (± 85) μm (P < .001) even though both groups had similar myopic refractive error. The scleral thickness 3000 μm temporal to the fovea was not different in the 2 groups. CONCLUSIONS Dome-shaped macula is the result of a relative localized thickness variation of the sclera under the macula in highly myopic patients, and it cannot be categorized into any of the known types of staphyloma. This finding suggests the ocular expansion in myopia may be more complex than previously thought.

Long-term follow-up for type 1 (subretinal pigment epithelium) neovascularization using a modified "treat and extend" dosing regimen of intravitreal antivascular endothelial growth factor therapy.

Purpose: The purpose of the study was to analyze long-term outcomes for the treatment of type 1 (subretinal pigment epithelium) neovascularization using a modified “treat and extend” antivascular endothelial growth factor dosing regimen. Methods: We performed a retrospective, noncomparative analysis of visual acuity, funduscopic, and optical coherence tomography data for 18 eyes of 16 consecutive patients with newly diagnosed type 1 neovascularization treated with intravitreal bevaci-zumab and/or ranibizumab with at least 24-month follow-up. Three monthly injections were followed by continued treatment at intervals increasing by 2 weeks per visit to a maximum of 10 weeks. The interval was shortened if clinical or optical coherence tomography evidence of recurrent fluid at the foveola or increased extrafoveolar fluid was detected. Results: Median baseline logarithm of the minimum angle of resolution visual acuity was 0.53 (20/69 Snellen equivalent) and remained stable at 24 months (logarithm of the minimum angle of resolution 0.52, P = 0.84) after an average of 12 injections (range, 8-19 injections) and at 36 months (logarithm of the minimum angle of resolution 0.52, P = 0.68) after an average of 20 injections (range, 18-25 injections). Although most eyes (15 of 18 [83%]) continued to manifest extrafoveolar subretinal fluid throughout the course of treatment, only 1 eye developed geographic atrophy overlying the areas of choroidal neovascularization. During a cumulative observation period of 540 months, no eyes developed a sight-threatening submacular hemorrhage. Conclusion: A modified “treat and extend” dosing regimen of intravitreal antivascular endothelial growth factor therapy reduces the need for monthly visits and imaging and allows for stable long-term visual acuity in eyes with type 1 neovascularization.

Acquired Vitelliform Lesions: correlation of clinical findings and multiple imaging analyses.

Purpose: To correlate clinical observations with multimodal imaging analysis in acquired vitelliform lesions (AVLs) and to elucidate their nature, pathogenesis, and natural course. Methods: Clinical examination, color fundus photography, fluorescein angiography, near-infrared reflectance, fundus autofluorescence, and spectral-domain optical coherence tomography (SD-OCT) data were retrospectively reviewed for a consecutive series of 90 eyes of 67 patients with an AVL secondary to a variety of diagnoses. Results: In all 90 eyes with AVLs, SD-OCT helped localize the clinically apparent yellowish material to the subretinal space above the retinal pigment epithelial (RPE) band. Only 19 eyes (21.1%) had SD-OCT evidence of subretinal fluid. All eyes exhibited abnormal hyperautofluorescence corresponding to the material seen clinically. In 18 of 72 eyes (25.0%) imaged simultaneously with SD-OCT and near-infrared reflectance imaging, near-infrared hyperreflectivity corresponding to presumed collections of pigment-laden macrophages and RPE cells was observed. Resolution of some AVLs appeared to coincide with progressive thinning of the outer nuclear layer, indicating a gradual loss of photoreceptors. Visual acuity at baseline was best predicted by the subfoveal integrity of the external limiting membrane (P = 0.001) and the inner segment/outer segment junction (P = 0.0002) on SD-OCT. Fluorescein angiography revealed a pattern often mimicking poorly defined (Type 1) choroidal neovascularization. Conclusion: Acquired vitelliform lesions occur in a variety of different clinical entities that share common features with multimodal imaging analyses. We propose that both dysfunctional RPE and loss of apposition between the photoreceptor tips and the RPE can interfere with the phagocytosis of shed outer segments. Both this material and pigment-laden macrophages and RPE cells appear to contribute to the yellowish appearance of AVLs. Ongoing photoreceptor loss may in some cases be associated with the spontaneous resolution of an AVL.

Segregation of ophthalmoscopic characteristics according to choroidal thickness in patients with early age-related macular degeneration.

Purpose: To investigate the association of fundus features with choroidal thickness in eyes with early age-related macular degeneration. Methods: Consecutive patients with age-related macular degeneration were evaluated. Major exclusionary criteria included late age-related macular degeneration (central geographic atrophy or choroidal neovascularization), macular laser therapy, myopia greater than −6 diopters, past vitreoretinal surgery, or central serous chorioretinopathy. Charts and multimodal imaging were reviewed for refraction, cataract, hypertension, diabetes, open-angle glaucoma, &bgr;-zone peripapillary atrophy, fundus tessellation, pigmentary changes, drusen, subretinal drusenoid deposits (also known as reticular pseudodrusen). Data measured from enhanced-depth imaging spectral-domain optical coherence tomography included subfoveal choroidal thickness, central foveal thickness, outer nuclear layer thickness, inner segment to retinal pigment epithelium aggregate thickness, presence of subretinal drusenoid deposit, and outer retinal hyperreflective layers (including the band corresponding to overlap between retinal pigment epithelium apical processes and outer segments). Correlations were calculated among the measured variables, fundus features, open-angle glaucoma, and visual acuity. Results: In 90 eyes of 70 early age-related macular degeneration patients with mean visual acuity 20/31 (logarithm of the minimum angle of resolution 0.193), subfoveal choroidal thickness showed a significant inverse correlation with age (P = 0.004) and increasing myopic spherical equivalent refractive error (P = 0.023). Subfoveal choroidal thickness was thinner in eyes with fundus tessellation (P < 0.001), subretinal drusenoid deposit (P = 0.023), an absence of conventional drusen (P < 0.001), the presence of &bgr;-zone peripapillary atrophy (P < 0.001), and in eyes with a diagnosis of open-angle glaucoma (P = 0.003) or an absent band on optical coherence tomography corresponding to overlap between outer segment and retinal pigment epithelium apical processes (P = 0.022). Conclusion: Major ocular manifestations in early age-related macular degeneration and open-angle glaucoma are associated with the choroid—the main blood supply in the eye. Theories concerning the pathogenesis of these two diseases should incorporate interactions involving the choroid.

High-resolution optical coherence tomography findings in optic pit maculopathy.

Purpose: The purpose of this study was to characterize retinal manifestations of optic pit maculopathy using high-resolution optical coherence tomography. Methods: Consecutive patients with optic pit maculopathy, diagnosed by their typical appearance by ophthalmoscopy, were imaged by color fundus photography and optical coherence tomography. The location and characteristics of any fluid within and under the retina were determined. Results: The mean age of the 16 patients (7 women) was 35.9 years (standard deviation: 18.5 years). The visual acuity ranged from 20/20 to 20/1000 (median, 20/200). Retinal detachment was found in 11 eyes (69%), intraretinal fluid in the outer nuclear layer in 15 eyes (94%), in the inner nuclear layer in 13 eyes (81%), in the ganglion cell layer in 7 eyes (44%), and in the subinternal limiting membrane space in 2 eyes (13%). An outer layer hole was identified in only 3 of 11 eyes (27%) with retinal detachment. Conclusion: Fluid from the optic pit can go directly to the subinternal limiting membrane space, ganglion cell layer, inner nuclear layer, outer nuclear layer, or the subretinal space, although the outer nuclear layer is most commonly affected. An outer layer hole appears not to be common in optic pit maculopathy.