Assessment of the microvasculature in poppers maculopathy.

PURPOSE: To investigate a possible microvascular component of poppers maculopathy (PMP) using optical coherence tomography angiography (OCTA). METHODS: Twelve patients suffering from poppers maculopathy were included. Health records, optical coherence tomography (OCT), and OCTA data was gathered and compared to a healthy control group (HC). PMP lesion type was determined by manifestation in OCT. OCTA-based evaluation of retinal vascular plexus and choriocapillaris (CC) was executed. Vessel density (VD) and vessel length density (VLD) in superficial and deep capillary plexus (SCP, DCP), as well as flow deficits (FD), within the foveal avascular zone (FAZ) in CC were assessed. RESULTS: Median age of PMP patients was 40 (min 24; max 64) years, all male. Eleven patients presented with ellipsoid zone-type lesions; one patient showed a vitelliform-type lesion. No qualitative microvascular changes between PMP patients and HC were identified. Quantitative values for VD and VLD of SCP and DCP did not differ in between the two groups. The analysis of FDs in CC showed no deviation from PMP patients to HC. CONCLUSIONS: No vascular anomalies in qualitative and quantitative analysis in OCTA were detected in PMP patients. The constitution of the CC within FAZ of PMP patients does not differ from HC when assessed as FD.

Optical coherence tomographic angiography shows reduced deep capillary flow in paracentral acute middle maculopathy.

INTRODUCTION: Paracentral acute middle maculopathy (PAMM) has been described as an ischemic lesion of the middle retinal layers with a characteristic lamellar hyper-reflective placoid appearance in the acute phase and thinning of the involved retinal layers in the chronic phase. Optical coherence tomographic angiography (OCTA) is a novel and non-invasive technique for imaging retinal capillary vasculature with en face segmentation capabilities. METHOD: Case series. We describe two patients with PAMM who underwent clinical examination and multimodal imaging including OCTA. RESULTS: In the first patient, who presented with PAMM secondary to acute cilioretinal artery occlusion, OCTA demonstrated reduction in flow in the deep capillary plexus (DCP). One month later, OCTA revealed a flow void due to thinning of the GCL, INL, and OPL and paradoxical apparent ONL thickening. Similar findings of focal retinal lamellar ectopia were seen in the second patient, who had an incidentally detected chronic PAMM lesion. CONCLUSIONS: OCTA images the superficial and deep capillary plexi independently. PAMM is characterized by acute and chronic attenuation of the DCP flow signature. Focal lamellar ectopia in PAMM is discussed.

En face OCT angiography demonstrates flow in early type 3 neovascularization (retinal angiomatous proliferation).

INTRODUCTION: The characteristics of type 3 neovascularization (NV), also known as retinal angiomatous proliferation, have been well described clinically, as well as with fluorescein angiography (FA), indocyanine green angiography, and optical coherence tomography (OCT). OCT angiography (OCT-A) is a novel and non-invasive technique for imaging retinal microvasculature by detecting changes, with respect to time, in reflectivity related to blood flow. METHOD: In this case series, we describe two patients who presented with type 3 NV and underwent clinical examination and multimodal imaging, including OCT-A. RESULTS: In the first patient, OCT-A demonstrated flow within two separate lesions in the same eye, one of which was only weakly detected by FA. In the second patient, sequential OCT-A demonstrated a reduction in intralesional flow following intravitreal therapy. CONCLUSIONS: OCT-A may have a role in the early diagnosis of type 3 NV and in assessing the response to treatment. Further studies are needed to determine sensitivity and specificity.

Pilot study to evaluate the role of high-dose ranibizumab 2.0 mg in the management of neovascular age-related macular degeneration in patients with persistent/recurrent macular fluid <30 days following treatment with intravitreal anti-VEGF therapy (the LAST Study).

PURPOSE: To determine the efficacy of intravitreal ranibizumab 2.0 mg in patients with recalcitrant neovascular age-related macular degeneration (AMD). METHODS: This single-masked, randomized, prospective, pilot study enrolled patients with subfoveal neovascular AMD. All study eyes had persistent subretinal (SRF) or intraretinal fluid (IRF) on spectral-domain optical coherence tomography (SD-OCT) <30 days following at least 6 monthly intravitreal injections of ranibizumab or bevacizumab. Patients were randomized 2 : 1 to receive either ranibizumab 2.0 or 0.5 mg. Following three-loading treatments 4-weeks apart, both groups were treated using a 'treat and extend' regimen guided by eye-tracked SD-OCT through month 12. The primary end point was the mean change in best-corrected visual acuity (BCVA) at month 6. RESULTS: Nine eyes of 9 patients (mean age ± SD, 82.0 ± 5.8 years) were enrolled. Seven eyes received ranibizumab 2.0 mg and two eyes received 0.5 mg. Owing to the small number of patients enrolled, no statistical comparison could be made between the two dosages. At month 6, the mean improvement in BCVA was +6.1 ± 3.7 (W=0, P<0.001) ETDRS letters and +2.0 ETDRS letters in the 2.0 and 0.5 mg groups, respectively. In the 2.0 mg group, there was a statistically significant decline in central foveal thickness, SRF and maximum pigment epithelial detachment height at 6 months compared with baseline. No adverse events were reported in either group. CONCLUSION: Ranibizumab 2.0 mg has the potential to maintain or improve BCVA in some patients with persistent or recurrent SRF or IRF secondary to neovascular AMD despite prior monthly intravitreal anti-vascular endothelial growth factor therapy with the standard dose.

Retinal angiomatous proliferation in age-related macular degeneration.

BACKGROUND: It is known that choroidal neovascularization (CNV) in age-related macular degeneration (ARMD) may erode through the retinal pigment epithelium, infiltrate the neurosensory retina, and communicate with the retinal circulation in what has been referred to as a retinal-choroidal anastomosis (RCA). This is extremely common in the end stage of disciform disease. In recent years, the reverse also seems to be possible, as angiomatous proliferation originates from the retina and extends posteriorly into the subretinal space, eventually communicating in some cases with choroidal new vessels. This form of neovascular ARMD, termed retinal angiomatous proliferation (RAP) in this article, can be confused with CNV. PURPOSE: The purpose of this article is 1) to review the clinical and angiographic characteristics of a series of patients with RAP and 2) to propose a theoretical sequence of events that accounts for the neovascularized process. METHODS: In this retrospective clinical and angiographic analysis, 143 eyes with RAP (108 patients) were reviewed and classified based on their vasogenic nature and course. Clinical biomicroscopic examination, fluorescein angiography, and indocyanine green angiography were used to evaluate patients. RESULTS: The results of this series suggest that angiomatous proliferation within the retina is the first manifestation of the vasogenic process in this form of neovascular ARMD. Dilated retinal vessels and pre-, intra-, and subretinal hemorrhages and exudate evolve, surrounding the angiomatous proliferation as the process extends into the deep retina and subretinal space. One or more dilated compensatory retinal vessels perfuse and drain the neovascularization, sometimes forming a retinal-retinal anastomosis. Fluorescein angiography in these patients usually revealed indistinct staining simulating occult CNV. Indocyanine green angiography was useful to make an accurate diagnosis in most cases. It revealed a focal area of intense hyperfluorescence corresponding to the neovascularization ("hot spot") and other characteristic findings. Based on understanding of the nature and progression of the neovascularized process, patients with RAP were classified into three vasogenic stages. Stage I involved proliferation of intraretinal capillaries originating from the deep retinal complex (intraretinal neovascularization [IRN]). Stage II was determined by growth of the retinal vessels into the subretinal space (subretinal neovascularization [SRN]). Stage III occurred when CNV could clearly be determined clinically or angiographically. A vascularized pigment epithelial detachment and RCA were inconsistent features of this stage. CONCLUSIONS: Retinal angiomatous proliferation appears to be a distinct subgroup of neovascular ARMD. It may present in one of three vasogenic stages: IRN, SRN, or CNV. Whereas ICG angiography is helpful in diagnosing RAP and in documenting the stage of the neovascularized process, it is frequently difficult to determine the precise nature and location of the new vessel formation. It is important for clinicians to recognize the vasogenic potential and the associated manifestations of this peculiar form of neovascular ARMD so that a proper diagnosis can be made, and when possible, an appropriate management administered.

Tamoxifen retinopathy in a male patient.

PURPOSE: To report a case of tamoxifen retinopathy in a male patient. METHODS: Case report. A 68-year-old man, who had received a cumulative tamoxifen dose of 60 g over 33 months for unresectable hepatocellular carcinoma, was evaluated. RESULTS: A peculiar, bilateral, symmetric, inner retinal crystalline deposition associated with mild macular edema was discovered. No other ocular toxicity of tamoxifen was observed. CONCLUSION: To our knowledge, this is the first report of tamoxifen retinopathy in a male.

Endoscopic vitreoretinal surgery for complicated proliferative diabetic retinopathy.

PURPOSE: To evaluate the indication for endoscopic vitreoretinal surgery in proliferative diabetic retinopathy (PDR). METHODS: Chart review of consecutive cases of vitreoretinal surgery for PDR performed by one of the authors (Y.L.F.) over a 2-year period. RESULTS: Endoscopic vitreoretinal surgery was performed in 8 of 41 (19.5%) eyes. The surgical indications were small pupil (3), hyphema (3), pseudophakia with fibrotic posterior capsule (1), and pars plana neovascularization with anterior tractional retinal detachment (6). CONCLUSION: Endoscopic vitreoretinal surgery, by enhancing the visualization of the retroirideal space, is a useful technique in PDR with opaque ocular media and/or neovascularization of the pars plana and ciliary body.

Retinal choroidal anastomoses and occult choroidal neovascularization in age-related macular degeneration.

OBJECTIVE: This study was designed to identify the incidence of retinal choroidal anastomoses in patients with occult choroidal neovascularization (CNV) and focal hot spots on indocyanine green (ICG) angiography, to identify the clinical and angiographic features that would assist in their identification, and to determine if the presence of these anastomotic lesions affect the outcome of laser therapy. DESIGN: Combined prospective and retrospective cross-sectional study. PARTICIPANTS: One hundred fifty consecutive patients with newly diagnosed occult CNV secondary to exudative age-related macular degeneration and focal hot spots on ICG angiography were evaluated prospectively. In addition, a retrospective review was performed on 79 eyes previously reported to have undergone laser photocoagulation treatment with ICG guidance. METHODS AND TESTING: In all cases, stereo color and red-free photographs, and stereo fluorescein and digital ICG angiograms were obtained for evaluation. MAIN OUTCOME MEASURES: Images obtained by all four techniques were evaluated for the presence of a retinal choroidal anastomosis. Associated clinical and angiographic findings were noted. In the retrospective review, the success rate of laser treatment was correlated with the presence or absence of a retinal choroidal anastomosis. RESULTS: Of the 150 eyes evaluated prospectively, 31 (21%) were found to have a retinal choroidal anastomosis. Retinal choroidal anastomoses were found in 27% of patients with associated serous pigment epithelial detachment (PED), whereas 13% were found in those without an associated elevation of the retinal pigment epithelium. Seventy-one percent of eyes had multiple anastomotic connections. Ninety percent of eyes had at least one retinal vein involved in the anastomotic connection. Clinical evidence of preretinal and intraretinal hemorrhage and cystic edema coupled with angiographic evidence of intraretinal dye leakage were key features of retinal choroidal anastomoses. In the retrospective review, seven patients were found to have retinal choroidal anastomoses with associated serous PED and demonstrated a very low (14%) success rate for laser treatment. CONCLUSIONS: Retinal choroidal anastomoses can present as a primary manifestation of the exudative process in age-related macular degeneration. They may be seen in eyes with and without detachment of the retinal pigment epithelium. Specific clinical and angiographic features have been identified that can aid in the diagnosis of these vascular anomalies. Their presence represents a poor prognostic sign for successful ICG-guided laser treatment.

Polypoidal choroidal vasculopathy masquerading as central serous chorioretinopathy.

OBJECTIVE: To differentiate polypoidal choroidal vasculopathy (PCV) from central serous chorioretinopathy (CSC). DESIGN: A retrospective, observational case series. PARTICIPANTS: Thirteen patients originally diagnosed with CSC proved to have PCV after more extensive evaluation and follow-up. METHODS: A clinical and angiographic review of patients with manifestations of CSC, including macular detachment. MAIN OUTCOME MEASURES: Demographic data, funduscopic examination, and fluorescein and indocyanine green (ICG) angiographic findings. RESULTS: Thirteen patients initially suspected of having CSC were ultimately diagnosed as having PCV. These eyes had exudative macular detachments secondary to a small caliber, polypoidal choroidal vascular abnormality or so-called polypoidal choroidal neovascularization. The clinical manifestations in the fundus varied. They included multiple, variably sized serous pigment epithelial detachments, neurosensory retinal detachment, lipid deposition, patchy atrophy of the pigment epithelium and indistinct staining from decompensation of the posterior blood-retinal barrier on fluorescein angiography. In reality, the suspected PEDs proved to be polypoidal lesions of PCV when imaged with ICG angiography. CONCLUSIONS: The clinical diagnosis of CSC or PCV generally poses little challenge to the experienced retinal specialist. However, in CSC with persistent and/or recurrent exudation, a myriad of retinal pigment epithelial changes may evolve that make it difficult to differentiate these two entities. In such patients, ICG angiography is useful in differentiating CSC from PCV. An accurate clinical diagnosis is important since each of these entities, CSC and PCV, may differ in terms of their risk factors, natural course, and visual prognosis.

Radiation exposure: a new risk factor for idiopathic perifoveal telangiectasis.

OBJECTIVE: To examine the association between previous radiation exposure and idiopathic perifoveal telangiectasis (IPT). DESIGN: A multicentered, individually matched, case-control study design was used. PARTICIPANTS/CONTROLS: Sixty-five case subjects were matched with 175 control subjects. Individuals with unequivocal evidence of angiographically confirmed IPT were included as cases. Control subjects were matched for center, age, and gender. MAIN OUTCOME MEASURE: The main exposures of interest were a history of therapeutic head or neck irradiation and environmental radiation exposure. METHODS: A standardized questionnaire was administered to case and control subjects. Data were collected for the main exposures of interest as well as pertinent covariates. Conditional logistic regression was used to evaluate therapeutic and environmental radiation as risks for IPT. RESULTS: On univariate analysis, head or neck irradiation was associated with IPT (odds ratios [OR] = 4.15, 95% confidence interval [CI] = 1.30-13.24). While controlling for diabetes and family history of diabetes, IPT was found to be associated with both head or neck irradiation (OR = 4.06, 95% CI = 1.20-13.76) and with environmental irradiation (OR = 6.73, 95% CI = 1.06-42.74). CONCLUSIONS: This study presents a previously unreported association between prior radiation exposure and IPT.

Radiation-associated choroidal neovasculopathy.

PURPOSE: To characterize a newly discovered choroidal vascular abnormality in patients who have received radiation therapy for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration. DESIGN: Two-center cross-sectional study. PARTICIPANTS: In the United States, there were 95 patients who were treated with 10 or 12 Gy of external beam photons. In Belgium, 98 patients were treated with 20 Gy. These patients were examined retrospectively for the presence of a specific CNV abnormality. RESULTS: During the follow-up period, an unusual vascular growth pattern was identified in 12 patients (12.6%) of those treated in the United States and in 7 (7.1%) of those treated in Belgium. These patients developed round or oval vascular blebs along the outer border of their neovascular lesions. These blebs profusely leaked fluorescein dye and could be imaged best by indocyanine green angiography. Patients with these blebs appeared to have a marked propensity for loss of visual acuity. CONCLUSION: An unusual pattern of new vessel growth occurred in 19 of the 193 patients with CNV treated with radiation. This new entity, termed radiation-associated choroidal neovasculopathy, is a recognizable disorder that appears to have a particularly poor prognosis.

Polypoidal choroidal vasculopathy and neovascularized age-related macular degeneration.

OBJECTIVE: To determine the nature and frequency of polypoidal choroidal vasculopathy (PCV) in a series of patients suspected of having neovascularized age-related macular degeneration (AMD). METHODS: A prospective analysis of 167 consecutive, newly diagnosed patients aged 55 years or older with presumed neovascularized AMD was performed. All patients were examined with fundus biomicroscopy as well as fluorescein and indocyanine green angiography. RESULTS: Choroidal neovascularization secondary to AMD was diagnosed in 154 (92.2%) of 167 patients; 13 (7.8%) patients had PCV. The patients affected by PCV were younger than those with AMD (P = .01). Peripapillary choroidal neovascularization was seen in 3 (1.9%) of 154 patients with AMD and 3 (23.1%) of 13 patients with PCV (P = .006). Significant drusen were present in 63 (70%) of 90 fellow eyes with unilateral AMD compared with only 1 (16.7%) of 6 eyes with PCV (P = .02). Only 5 patients with AMD (3.2%) were nonwhite compared with 3 patients with PCV (23.1%) (P = .02). CONCLUSIONS: A measurable number of elderly patients with findings suggestive of neovascularized AMD and serosanguineous macular manifestations will instead have PCV. Polypoidal choroidal vasculopathy can occur in any sex or race, but is more commonly seen in the peripapillary area, without associated drusen, and in nonwhite patients. It is important to differentiate AMD from PCV because there are significant differences in the demographic risk profile, natural course, visual prognosis, and management of these patients.

Indocyanine-green videoangiography of drusen as a possible predictive indicator of exudative maculopathy.

OBJECTIVE: Recent studies have shown that indocyanine-green videoangiography (ICG-V) is useful to image occult choroidal neovascularization. The authors studied the ICG-V findings in fellow drusen eyes of patients with unilateral exudative age-related macular degeneration (AMD). The authors also studied the occurrence of exudative changes to determine whether ICG-V is useful in predicting future exudative changes in these eyes with only drusen. DESIGN: Cohort study. PARTICIPANTS: The authors studied 432 consecutive patients diagnosed with unilateral exudative AMD in whom the fellow eye had only drusen by clinical fundus examination and fluorescein angiography. All of these eyes had ICG-V performed. Follow-up data were obtained in all eyes with abnormal indocyanine-green (ICG) angiograms and randomly sampled ICG angiograms of normal eyes. MAIN OUTCOME MEASURES: The initial ICG findings were classified as showing normal or abnormal hyperfluorescence. Abnormal hyperfluorescence eyes were subdivided into focal spots (focal areas of hyperfluorescence < 1 disc area in size) and plaques (areas of hyperfluorescence > 1 disc area). The development of exudative changes in eyes with normal and abnormal hyperfluorescence was compared. RESULTS: Of the 432 fellow eyes, 386 (89%) eyes with drusen had a normal ICG-V study, whereas 46 (10 focal spots and 36 plaques) (11%) eyes had an abnormal ICG-V. Exudative changes occurred in 6 (10%) of 58 normal ICG eyes and 9 (24%) of 38 eyes with abnormal ICG findings during a mean follow-up period of 21.7 months. The difference between drusen eyes with normal ICG angiograms and those with plaques on ICG-V regarding future exudative changes (10% vs. 27%, respectively) was statistically significant (P = 0.038). CONCLUSIONS: Abnormal ICG findings were found in 11% of eyes with clinically and fluorescein angiographically nonsuspicious drusen. The subgroup of patients with plaques on ICG-V had a higher chance of having exudative changes develop. Indocyanine-green videoangiography may be a predictive indicator of future exudative changes in eyes with drusen. A much larger prospective study seems justified.

Factor V Leiden, activated protein C resistance, and retinal vein occlusion.

BACKGROUND: Resistance to activated protein C (APC resistance) is a thrombophilic abnormality characterized by a normal plasma level of protein C and an inherited defect in the coagulative response. This condition is believed to be caused by a point mutation in factor V, the so-called factor V Leiden, and is inherited as an autosomal dominant trait. PURPOSE: A case-control study was carried out to evaluate the prevalence of APC resistance and factor V Leiden in patients with retinal vein occlusion (RVO) and in control subjects. METHODS: Eighty-four consecutive RVO patients and 70 controls were tested for APC resistance with a commercial assay (Chromogenix). The first 30 patients and 47 controls were also studied for factor V Leiden. In addition, a repeat APC-resistance test was performed in 40 RVO patients and in 9 controls with a second-generation assay done to compare the reliability and reproducibility of the tests. RESULTS: Results of testing for APC resistance with the first-generation assay revealed positive results in 38 (45%) of the study patients and 6 (9%) of the controls. The difference in frequencies of APC resistance in patients and controls was statistically significant (P < 0.0001). In the patients tested for factor V Leiden, one (3%) was a heterozygous carrier of the Arg506GIn mutation and one (2%) of the controls was a heterozygous carrier. No homozygous individuals were identified in either the study or the control groups. The difference in frequencies of factor V Leiden in study patients and controls was not statistically significant (P = 1). The repeat APC-resistance assay using factor V-deficient plasma in 40 RVO patients and 9 controls did not show any significant difference between study patients and controls or an association between APC resistance and the determination of the factor V Leiden mutant. CONCLUSION: The first-generation commercial assay for APC resistance is not a useful screening test. The molecular test for factor V Leiden is the only definitive method. Furthermore, no significant association was found between factor V Leiden and retinal vein occlusion. Accordingly, routine testing for the presence of the factor V Leiden mutant is not advisable for patients with retinal vein occlusion.

Wide-angle indocyanine green angiography.

BACKGROUND: Evaluation of the vasculature and blood flow in the fundus is limited by the small field of view of conventional fundus cameras. We sought to develop an easy method to image wide areas of the fundus. METHODS: Wide-angle contact fundus lenses with antireflective coatings in the infrared range were placed on the eye and indocyanine green angiography was done on the fundus through the contact lenses. More than 50 patients with varying fundus pathology have been examined. RESULTS: The angular field of view using this method can reach 160 degrees. Obtaining angiograms where the field of view extended anterior to the ora serrata was simplified, and studying the choroidal vasculature in detail was possible. In addition, imaging of entities such as peripheral choroidal neovascularization and choroidal tumors was enhanced with the present technique as compared with conventional techniques. CONCLUSIONS: Angiography through wide-angle fundus lenses is an easy and inexpensive method of visualizing large areas of the fundus. This technique may help improve our ability to image the angioarchitecture, hemodynamics, and pathologic changes in the retina and choroid.