Topography of choriocapillaris flow deficit predicts development of neovascularization or atrophy in age-related macular degeneration

Graefe's Archive for Clinical and Experimental Ophthalmology - To evaluate the relationship between choriocapillaris (CC), flow deficits (FD), and structural optical coherence tomography (OCT)...     

Clinical observations supporting a theoretical model of choriocapillaris blood flow in treatment of choroidal neovascularization associated with age-related macular degeneration

PURPOSE: To report clinical observations consistent with conclusions from a previous theoretical investigation indicating that photocoagulation of choroidal neovascularization (CNV) efferent vessels can be, in some instances, an effective treatment. DESIGN: Interventional case series. METHODS: In five eyes with age-related macular degeneration (five patients with mean age +/- SD of 65 +/- 11 years, range 55-79 years) requiring treatment of CNV. In each case, the appropriate treatment was location and photocoagulation of the CNV efferent vessels, since the afferent vessels were not identifiable or were located beneath the fovea. Targeted vessels were determined to be draining vessels by analysis of pretreatment high-speed indocyanine green (ICG) angiograms, and successful vessel closure by photocoagulation was demonstrated by posttreatment ICG angiograms. The eyes subsequently were followed from 2 to 12 months. RESULTS: After photocoagulation of efferent vessels, CNV-related retinal edema was significantly reduced or resolved within 1 to 4 days. Visual acuity became stabilized in three eyes and improved in two eyes. In a few days, metamorphopsia disappeared in four of the eyes and was stable for a period longer than the duration of the associated efferent vessel closure. Initial efferent vessel closure by photocoagulation persisted on average for 7 to 15 days, after which additional treatment was required. It is significant that in no case did hemorrhage result from the photocoagulation treatment. CONCLUSIONS: These observations are consistent with the earlier theoretical study prediction that photocoagulation of efferent CNV vessels can be effective in reducing CNV-associated edema. That no hemorrhage was induced by photocoagulation is consistent with the theoretical concept that there appears to be no direct hydrostatic connection between the CNV and its afferent vessels. Rather, that connection appears to be a functional one made through the choriocapillaris, which may dissipate excess CNV hydrostatic pressure produced by occlusion of a draining vessel. However, this finding is not intended to be a recommendation to attempt CNV efferent vessel photocoagulation.     

Development of macular hole and macular retinoschisis in eyes with myopic choroidal neovascularization

PURPOSE: To determine whether the chorioretinal atrophy (ChRA) adjacent to a choroidal neovascularization (CNV) is related to the development of a macular hole or macular retinoschisis in highly myopic eyes. DESIGN: Observational case series. METHODS: One hundred and eighty-one eyes of 125 patients with high myopia were divided into three groups: group 1 had a myopic CNV surrounded by ChRA larger than 1 disk area (43 eyes), group 2 had a myopic CNV surrounded by a ChRA smaller than 1 disk area (45 eyes), and group 3 did not have CNV (93 eyes). Optical coherence tomography (OCT) was used to evaluate the macular morphologic features, for example, macular holes and macular retinoschisis. RESULTS: A macular hole was detected by OCT in six eyes (14%) in group 1 and in none of the eyes in groups 2 and 3. The hole always existed at the border between an old CNV and the surrounding ChRA. A macular retinoschisis was detected in four eyes (9%) in group 1 and in eight eyes (9%) in group 3. The macular retinoschisis seen in group 1 appeared markedly less column-like than those in group 3. It was somewhat difficult to differentiate a retinal detachment from retinoschisis in the eyes in group 1. CONCLUSIONS: Eyes at the atrophic stage of myopic CNV have a higher risk of developing a macular hole, and we recommend periodic OCT examinations for macular holes or macular retinoschisis, even in asymptomatic, highly myopic eyes, after the CNV has progressed to the atrophic stage.     

Theoretical investigation of the role of choriocapillaris blood flow in treatment of subfoveal choroidal neovascularization associated with age-related macular degeneration.

PURPOSE: To investigate the relationship between choriocapillaris blood flow and blood flow through an overlying choroidal neovascularization, as it relates to photocoagulation-induced changes in the choriocapillaris circulation. METHODS: A theoretical model that simulates the blood flow in the choriocapillaris and choroidal neovascularization of the human eye was developed, based on histologically determined vascular geometry and experimentally measured blood pressure gradients. The choriocapillaris blood pressure and blood flow were examined before and after simulated photocoagulation of various Sattler layer vessels entering the choriocapillaris in the vicinity of the choroidal neovascularization. (The Sattler layer is the inner layer of medium-sized choroidal vessels that includes both arterioles and venules that supply the choriocapillaris.) RESULTS: The theoretical model showed that both partial and complete occlusion of either Sattler arteriole or venous vessels in the vicinity of the capillary-like vessels connecting a choroidal neovascularization to the underlying choriocapillaris results in significant choroidal neovascularization blood flow reduction. These theoretical results are similar to clinically observed changes induced by laser photocoagulation of feeder vessels. (In this discussion, the term "feeder vessels" refers to those vessels in an indocyanine green angiogram image that appear to supply blood to a choroidal neovascularization; these vessels appear to be Sattler layer vessels, rather than the histologically demonstrated short, capillary-like vessels that form choriocapillaris-choroidal neovascularization communications.) CONCLUSIONS: Reduction of choriocapillaris blood flow underlying a choroidal neovascularization may be sufficient to reduce the blood flow rate in the choroidal neovascularization and thereby reduce the associated retinal edema. The results also suggest that reduction of choriocapillaris blood flow may be the common hemodynamic event associated with the successful application of several currently practiced methods of choroidal neovascularization treatment, including feeder vessel photocoagulation, photodynamic therapy, transpupillary thermotherapy, and prophylactic drusen photocoagulation. Ultimately, this model may be useful in determining optimal placement of laser photocoagulation burns to achieve a desirable perturbation in choroidal blood flow distribution and thereby reduce choroidal neovascularization blood flow to the extent necessary to obliterate associated retinal edema.     

Short-term reaction of choroidal neovascularization and choriocapillaris to photodynamic therapy in age-related macular degeneration

PURPOSE: To identify the number of primary angiographic nonresponders to photodynamic therapy (PDT) with verteporfin, to determine the rate and speed of reperfusion of choroidal neovascularization (CNV) within a short observation period of only 5 weeks, and to examine the reaction of the underlying choroidal vessels. METHODS: PDT according to the TAP regimen was carried out in 36 eyes with subfoveal classic CNV secondary to age-related macular degeneration. The response to PDT was examined 1 (T1) and 5 (T2) weeks following treatment. At all visits distant visual acuity was measured and both fluorescein and indocyanine green angiography was carried out. RESULTS: One week after treatment (T1), complete closure of classic CNV had not been achieved in 17% of eyes (primary angiographic nonresponders). At T2, 91% of eyes showed reperfusion of the CNV. In 83% of the primary angiographic nonresponders the CNV size was larger than before treatment. Choroidal shadowing was present in 82% at T1 and in 48% at T2. CONCLUSIONS: Primary angiographic PDT nonresponders are relatively rare; however, in contrast to former reports, they exist and can be identified by follow-up examination 1 week after PDT. Recurrence of leakage occurred earlier than expected and may require closer follow-up and earlier retreatment than recommended by the TAP trial.     

Management of eyes with both idiopathic macular hole and choroidal neovascularization.

PURPOSE: To describe the characteristics, treatment, and outcome of five eyes with both choroidal neovascularization (CNV) and macular hole. METHODS: Medical records of five patients with both macular hole and CNV were reviewed. RESULTS: All eyes had full-thickness macular holes. Most eyes had atypical-appearing macular holes (subretinal hemorrhage, prominent subretinal fluid, or discoloration at the hole margin) at presentation or subsequently when CNV developed. Fluorescein angiography (FA) confirmed the presence of CNV in each eye. Three eyes underwent combined macular hole repair and CNV removal, and sustained closure of these macular holes was achieved. A fourth eye underwent successful argon laser photocoagulation of extrafoveal CNV, and macular hole surgery was declined. The final eye underwent two macular hole repairs before sustained closure was achieved. Final visual acuity, ranging from 20/100 to hand motions, was limited by macular pathology and/or cataract. CONCLUSIONS: Choroidal neovascularization can occur in association with a macular hole. In eyes with an atypical-appearing macular hole, FA should be obtained to detect CNV. Excision of the CNV can be done safely in conjunction with macular hole surgery. Final visual acuity may be limited by cumulative retinal and retinal pigment epithelium damage, especially in eyes with underlying macular disease.     

The choriocapillaris in the macular area

Fluorescein fundus angiographies performed with the Cannon wide-angle fundus camera enable a good vascular definition, which improves our knowledge of the choroidal circulation. Owing to the better quality of filters, the choroidal arteriolar network can be seen more precisely. Our recent studies have enabled us to confirm the existence of a special avascular area in the central part of the submacular choroid, surrounded by a perimacular choriocapillaris ring. In the macular area, the choriocapillaris corresponds to a thin layer which is most probably supplied by several arterioles from the short posterior ciliary arteries near their site of entry into the eyeball. As stated by Hayreh, there may be a central area where the capillary pressure, while being well balanced, is very low.     

Relationship between proximity of choriocapillaris flow deficits and enlargement rate of geographic atrophy

Graefe's Archive for Clinical and Experimental Ophthalmology - To correlate choriocapillaris (CC) flow deficits (FD) in eyes with geographic atrophy (GA) at various distances from the border of...     

Treatment of juxtafoveal choroidal neovascularization with photodynamic therapy using verteporfin in eyes with age-related macular degeneration.

To report the results of treating juxtafoveal choroidal neovascularization with photodynamic therapy using verteporfin in eyes with age-related macular degeneration. Seven patients with predominantly classic juxtafoveal choroidal neovascularization were treated by photodynamic therapy using verteporfin. Three of the 7 patients had a gain in visual acuity and 2 had a stabilization of vision. The remaining 2 patients had a decrease in visual acuity. Subfoveal extension of the choroidal neovascularization was not observed in any patient and all choroidal neovascularization lesions after treatment were found to be nonperfused on fluorescein angiography. The encouraging results based on this small pilot study suggest that photodynamic therapy should be considered for treatment of select juxtafoveal choroidal neovascularization due to age-related macular degeneration.     

Fixation pattern and macular sensitivity in eyes with subfoveal choroidal neovascularization secondary to age-related macular degeneration. A microperimetry study

PURPOSE: To investigate the effects of subfoveal choroidal neovascularizzation (CNV) secondary to age-related macular degeneration (AMD) on macular functional parameters quantified with an automatic fundus perimeter. METHODS: 118 eyes of 98 consecutive patients with subfoveal CNV secondary to AMD were evaluated. Best corrected visual acuity (ETDRS charts), fundus photography, and fluorescein angiography were performed. Microperimetry (fundus-related perimetry) was used to quantify macular sensitivity and fixation pattern (location and stability). RESULTS: Of 118 eyes: 26 (21.9%) had central, 18 (15.1%) poor central and 74 (63.0%) eccentric fixation; 31 (26.0%) had stable, 42 (35.6%) relatively unstable and 45 (38.4%) unstable fixation. In 75 eyes (63.4%) a dense central scotoma was found. Angiographic classification of subfoveal CNV (occult versus classic) was not significantly related to fixation pattern (location: P = 0.274; stability: P = 0.385), and presence of dense scotoma (P = 0.41). CONCLUSION: Microperimetric quantification of macular sensitivity and fixation pattern in eyes with subfoveal CNV secondary to AMD offers new data about the impact of visual impairment in these eyes. Moreover, microperimetry improves the functional evaluation of subfoveal CNV in AMD.     

Fixation pattern and macular sensitivity in eyes with subfoveal choroidal neovascularization secondary to age-related macular degeneration. A microperimetry study

Purpose. To investigate the effects of subfoveal choroidal neovascularizzation (CNV) secondary to age-related macular degeneration (AMD) on macular functional parameters quantified with an automatic fundus perimeter. Methods. 118 eyes of 98 consecutive patients with subfoveal CNV secondary to AMD were evaluated. Best corrected visual acuity (ETDRS charts), fundus photography, and fluorescein angiography were performed. Microperimetry (fundus-related perimetry) was used to quantify macular sensitivity and fixation pattern (location and stability). Results. Of 118 eyes: 26 (21.9%) had central, 18 (15.1%) poor central and 74 (63.0%) eccentric fixation; 31 (26.0%) had stable, 42 (35.6%) relatively unstable and 45 (38.4%) unstable fixation. In 75 eyes (63.4%) a dense central scotoma was found. Angiographic classification of subfoveal CNV (occult versus classic) was not significantly related to fixation pattern (location: P = 0.274; stability: P = 0.385), and presence of dense scotoma (P = 0.41). Conclusion. Microperimetric quantification of macular sensitivity and fixation pattern in eyes with subfoveal CNV secondary to AMD offers new data about the impact of visual impairment in these eyes. Moreover, microperimetry improves the functional evaluation of subfoveal CNV in AMD.     

The development of choroidal neovascularization in eyes with the geographic atrophy form of age-related macular degeneration.

OBJECTIVE: To determine the rate of developing choroidal neovascularization (CNV) in eyes with geographic atrophy (GA) from age-related macular degeneration (AMD) and the characteristics of the CNV in these eyes. DESIGN: Prospective natural history study with cohort analysis. PARTICIPANTS: One hundred fifty-two patients with GA and no CNV by fluorescein angiography in at least 1 eye, with annual follow-up. MAIN OUTCOME MEASURES: The development of CNV. RESULTS: Thirteen eyes with GA developed CNV. For patients with bilateral GA and no CNV at baseline, 2% developed CNV by 2 years and 11% by 4 years. For patients with CNV in the fellow eye, 18% developed CNV in the study eye with GA by 2 years and 34% by 4 years. The eyes that developed CNV experienced more acuity loss than did the eyes with only GA. Within the fellow eye CNV group, those study eyes with GA that had less central atrophy (and better acuity) at baseline were more likely to develop CNV. The CNV developed at a peripheral border of GA in nine eyes, in the spared foveal region in two eyes, and in both center and border in one eye. No eye developed CNV in the area of atrophy itself. The appearance of CNV was evanescent in some cases and had a final appearance of an enlarged area of GA. Twelve other eyes had hemorrhages without definite evidence of CNV; three were thought to be suspicious for CNV and the remainder were thought to be hemorrhages that may be seen in elderly patients. CONCLUSION: An eye with GA whose fellow eye has CNV is at significant risk for the development of CNV in the GA eye. A patient with bilateral GA and no evidence of CNV is at relatively low risk for developing CNV. The CNV may be evanescent and may not be detected. Intraretinal hemorrhages unrelated to CNV are relatively common in this older population.     

Transpupillary thermotherapy for treatment of choroidal neovascularization secondary to age-related macular degeneration in Indian eyes

AIM: To evaluate the efficacy of transpupillary thermotherapy (TTT) for treatment of subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD), and to define accurate power settings for this procedure in Indian eyes. METHODS: A prospective, nonrandomised study of 160 eyes of 144 patients with subfoveal CNV. The laser settings included 2 mm spot and 300 mw power or 3 mm spot and 400-600 mw power. Two separate 3 mm spots were used in larger lesions. The treatment was given for 60 seconds at each point. RESULTS: Ninety-nine eyes had classic membranes and 61 eyes had occult membranes. Following treatment, 79 of 99 (79.8%) classic and 52 of 61 (85%) occult membranes regressed. Visual improvement (> or = 2 lines) was seen in 29 (29.3%) eyes and 12 (19.6%) eyes; visual stabilisation (1 line) in 39 (39.4%) eyes, and 35 (57.4%) eyes; and reduction of vision (< or = 2 lines) in 31 (31.3%) eyes and 14 (22.9%) eyes with classic and occult membranes respectively. Mean follow-up was 12 months. One patient suffered inadvertant foveal burn. CONCLUSION: TTT is effective in the management of subfoveal membranes in Indian eyes. They respond to lower energy levels compared to the Caucasian eyes.     

Reproducibility of qualitative assessment of drusen volume in eyes with age related macular degeneration

BackgroundAlthough an optical coherence tomography (OCT)-derived central drusen volume ≥0.03 mm³ has been found to be a risk factor for progression to late age-related macular degeneration (AMD), this parameter is not currently available on most OCT devices or acquisition protocols. The purpose of this study was to evaluate the ability of human graders to qualitatively assess drusen volume by inspection of OCT B-scans.Methods100 subjects (200 eyes) from the Amish Eye Study diagnosed with early or intermediate AMD underwent OCT imaging with both Cirrus OCT and Spectralis OCT. Drusen volume was automatically computed from the Cirrus OCT volumes using the Cirrus Advanced RPE Analysis software. Spectralis volume scans were reviewed by two independent, masked graders who were asked to determine whether the central drusen volume was ≥0.03 mm³. Cohen’s kappa coefficients were computed to assess the agreement.ResultsAfter excluding 11 eyes with poor image quality and 5 eyes used for training of the graders, the remaining 184 eyes were included in this analysis. The agreement between the graders and the automated evaluation of drusen volume by the Cirrus OCT was excellent with K = 0.88 for grader 1 and K = 0.82 for grader 2. The agreement between graders was also excellent with a K = 0.88.ConclusionsThe presence of a high central drusen volume can be assessed reliably by qualitative inspection of OCT B-scans. This approach may be useful in the assessment of risk for progression to late AMD.Subject terms: Macular degeneration, Eye diseases     

Quantitative assessment of structural damage in eyes with localized visual field abnormalities

PURPOSE: To evaluate the pattern of structural damage in the macula and peripapillary retinal nerve fiber layer (RNFL) using optical coherence tomography (OCT) and scanning laser polarimetry (SLP-VCC) in glaucomatous eyes with localized visual field defects. DESIGN: Prospective, cross-sectional analysis. METHODS: Complete examination, automated achromatic perimetry (AAP), Stratus OCT imaging (512 A-scans) of the peripapillary retina and macula, and SLP-VCC imaging of the peripapillary RNFL were performed. Thickness values in the retinal segments associated with the visual field defect (glaucomatous segments) were compared with corresponding segments across the horizontal raphe (nonglaucomatous segments) and age-matched normal controls. RESULTS: Forty eyes of 40 patients (20 normal, 20 glaucomatous) were enrolled (mean age, 71 +/- 10 years; range, 50 to 89). Mean RNFL thickness using SLP-VCC and OCT in the nonglaucomatous segments of glaucomatous eyes (54.0 +/- 9.7 microm, 64.7 +/- 19.0 microm) were significantly (P =.009, <0.0001) reduced compared with the thickness measurements in the corresponding segments of age-matched normal subjects (62.5 +/- 9.2 microm, 105.6 +/- 19.0 microm) respectively. No significant (P =.4) differences in the macular thickness measurements were observed between nonglaucomatous (239.0 +/- 19.4 microm) and normal segments (243.5 +/- 15.0 microm). Compared with age-matched controls, RNFL thickness in the nonglaucomatous segment was abnormal in 15 of 20 patients (75%) with SLP-VCC and in 18 of 20 patients (90%) with OCT. Macular thickness in the nonglaucomatous segment was abnormal in 11 of 20 patients (55%). CONCLUSIONS: Diffuse RNFL and retinal ganglion cell loss is present in eyes with localized visual field abnormalities. Detection of localized changes in macular thickness is limited by measurement overlap among normal and glaucomatous eyes.