Choroidal neovascularization, experimental and clinical study]

As a special lecture at the 95th annual Congress of the Japanese Ophthalmological Society in 1991, we presented experimental studies on choroidal neovascularization (ChNV), and clinical studies on senile disciform macular degeneration (exudative age-related macular degeneration). We produced experimentally ChNV on monkey eyes using intense photocoagulation with krypton laser. We showed the retinal pigment epithelium (RPE) played a heavy role as inducer or inhibitor for ChNV at different stages of development or involution of experimental ChNV. Senile disciform macular degeneration is becoming a leading cause of blindness in the elderly in Japan. We examined 473 eyes in 398 cases of this disease during the past 5 years. Nineteen percent were bilaterally affected, males were affected 3 times prevalent than in female, and average age was 67 in years. Predisposing signs were degeneration or atrophy of RPE, hard or soft drusen, and serous detachment of RPE in the macula. In early stage, serous retinal detachment stage appeared and showed good outcome by laser treatment. Subretinal hematoma form showed next better outcome in acute onset and acute course. Advanced form of disciform lesion showed worse outcome. A form (subretinal cystic form) associated with large serous RPE detachment showed the worst outcome and scarcely indicated for laser treatment. We describe clinical features of each form and stages of the disease and clinical course. Early detection, early correct diagnosis and early laser treatment must be essential for prevention of blindness due to this disease.     

Unilateral vitreous hemorrhage secondary to massive subretinal hemorrhage in 5 cases]

Massive subretinal and vitreous hemorrhage (MSVH) in the elderly is usually complicated with senile disciform macular degeneration (SDMD). The authors treated 5 cases, averaging 59 years old, with MSVH in unilateral eye. They noticed sudden loss of vision and underwent vitreous surgery. After operation, organized hematomas were seen beneath the retina, which disappeared without scar formation, leaving atrophic lesions of the RPE and neural retina. The final visual outcome was NLP to 0.8, depending upon the location of subretinal hemorrhage. Fluorescein angiography demonstrated no subretinal neovascularization. Contralateral eyes showed no sign of SDMD during follow-up period of up to 6.5 years. These cases may suggest a pathogenesis different from the hemorrhagic type of SDMD.     

Surgical occlusion of 2 vorticose veins in the treatment of decompensated senile macular degeneration

Surgical occlusion of two vortex veins was carried out on 9 eyes of 9 patients with complications associated with senile macular degeneration. 5 eyes had avascular detachment of the retinal pigment epithelium; 4 eyes had a disciform macular lesion with choroidal neo-vessels. The follow-up varies from 3 months to 2 years (average 10 months). At the end of the follow-up period the visual acuity was the same or better in the 5 eyes with a vascular detachment of the pigment epithelium. Metamorphopsia regressed in all eyes. Pigment epithelium detachment in 3 eyes, which happened 1 month to 3 months postoperatively, incomplete flattening of the pigment epithelium detachment in 1 eye and no modification in 1 eye. In the 4 eyes with choroidal neo-vessels the course of the disease was not modified.     

Macular lesions predisposing to senile disciform macular degeneration.

Senile disciform macular degeneration (SMD) is a neovascular/exudative form of age-related macular degeneration (AMD). In this study 340 eyes were followed up to assess the progression of SMD. The 340 eyes consisted of two groups. Group 1 was composed of 157 eyes with age-related macular changes other than choroidal neovascular membrane. Group 2 was made up of the contralateral eyes of 183 unilateral SMD eyes. Average ages were 61 and 64 in groups 1 and 2, respectively, and respective follow-up periods were 44 and 52 months. Choroidal neovascular membrane developed in 12 eyes in group 1 (7.6%) and in 19 eyes in group 2 (10.4%), a total of 31 eyes (9.1%). Retinal pigment epithelium (RPE) detachment was found as a predisposing lesion in 25 of these 31 eyes. Choroidal neovascular membrane developed in 12 of the 24 eyes with large RPE detachments. In 3 eyes neovascular membrane developed from an RPE detachment which had evolved from soft drusen. There were 3 eyes among the 62 eyes with soft drusen in which neovascular membrane developed directly from soft drusen. Based on these results, we classified AMD into 3 types; 1) atrophic, 2) predisciform, which includes RPE detachment and soft drusen, and 3) SMD.     

Bilateral midperipheral large drusen and retinal pigment epithelial detachments associated with multifocal areas of choroidal neovascularization: a histopathologic study

PURPOSE: The ocular histopathologic features of a patient with bilateral multiple midperipheral areas of choroidal vascularization, large drusen, and detachments of the retinal pigment epithelium (RPE) are presented. METHODS: The eyes were obtained at autopsy and fixed in 4% buffered formaldehyde. Serial sections through the macula area and inferior segments were prepared. Light as well as electron microscopy was performed. RESULTS: Microscopic examination disclosed numerous large drusen measuring up to 200 micro m in height and 280 micro m in diameter and areas of serous RPE detachments in the midperiphery of both eyes. Some of the large drusen had choroidal vascularization. Areas of sub-RPE neovascularization that measured up to 6.5 mm in diameter were present in the midperiphery of both eyes. The choroidal origin for neovascularization was evident in 10 areas. A 1-mm area of hemorrhagic detachment of the RPE contiguous with choroidal neovascularization (CNV) was present in the immediate postequatorial area temporally in the left eye. No drusen, basal deposit, or CNV was present in the macular area. CONCLUSION: Multifocal midperipheral RPE detachments and CNV can occur in the absence of significant age-related macular disease.     

Senile disciform macular degeneration complicated by massive hemorrhagic retinal detachment and angle closure glaucoma

Six eyes developed angle-closure glaucoma secondary to total hemorrhagic retinal detachment that occurred as a rare complication of senile disciform macular degeneration. The patients were all elderly with known senile macular choroidal degeneration. They had no history of eye surgery and experienced sudden loss of vision followed by pain. Balloons of retinal detachment were pushed tightly against the lens in a characteristic "Y suture" appearance causing shallowing of the anterior chamber and glaucoma. Pathologic examination of three eyes revealed that the choroid was not detached but that a massive subretinal hemorrhage was present. Neovascular tissue in macular disciform lesions was found in every case and was the probable source of hemorrhage. Sheets of avulsed retinal outer segments were seen incarcerated in subretinal blood in two cases, and drainage of this subretinal blood in three cases did not restore useful vision.     

Morphopathological study in age related macular degeneration

The aim of this paper is to study the morphopathological changes manifested in age-related macular degeneration. MATERIAL AND METHOD: The researched histopathological material consisted in two eye balls enucleated because of irreversible eye diseases from aged persons suffering from age-related macular degeneration. The method applied for processing the material was inclusion in paraffin, followed by usual coloration with hematoxylin-eosin. RESULTS AND CONCLUSIONS: The established changes (hard drusen, soft drusen, calcified drusen, changes of Bruch's membrane, subretinal neovascularization, serous retinal pigment epithelial detachment, disciform degeneration) prove the importance of Bruch's membrane in the pathogenesis of age-related macular degeneration.     

Siblings with age-related macular degeneration in a pedigree

BACKGROUND: The pathogenesis of age-related macular degeneration remains unknown. Environmental and genetic factors have been shown to be associated with in this disease. We report siblings with age-related macular degeneration. CASES: The proband (the third of 6 siblings) was found to have retinal pigment epithelial abnormalities and drusen of the right macula, and serous retinal detachment, drusen, and choroidal neovascularization of the left macula. Examination of the eldest siblings showed choroidal neovascularization, subretinal hemorrhage, and serous retinal detachment of the right macula. The left eye of the proband and the right eye of the eldest siblings were treated with laser photocoagulation. The fourth sibling was examined, and findings included retinal pigment epithelial abnormalities of both maculas and drusen of the right eye. The sixth sibling had drusen of the left macula. CONCLUSION: We report a family in which two siblings had age-related macular degeneration and two other siblings had abnormalities of the maculas.     

Retinal pigment epithelial tear following photodynamic therapy for choroidal neovascularization secondary to AMD

PURPOSE: To describe retinal pigment epithelial tear following photodynamic therapy (PDT) for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Retrospective interventional case series. METHODS: A retrospective study in an institutional practice. We describe seven cases of retinal pigment epithelial (RPE) tear, which developed in seven eyes of seven patients following PDT. All eyes had subfoveal CNV secondary to AMD. RESULTS: Six eyes had occult subfoveal CNV, and one eye had recurrent classic subfoveal CNV. In five patients, the eye that developed the tear was the second eye, whereas the first eye had a disciform scar. In four eyes, the RPE tear developed after one PDT, in one eye the RPE tear developed after the second PDT, and in two eyes the RPE tear developed after the third PDT. In five of seven cases, there was a significant visual deterioration following the RPE tear. CONCLUSIONS: RPE tear is a complication that may occur following PDT in particular when the PDT is applied to an occult subfoveal CNV.     

Photocoagulation of serous detachments of the retinal pigment epithelium in patients with senile macular disease

Twenty-one eyes of 18 patients aged 58 to 78 years (mean: 66 years) showing serous retinal pigment epithelial detachment associated with senile macular degeneration underwent green argon laser photocoagulation and were observed from 7 to 69 months (mean: 27 months). Treatment collapsed the retinal pigment epithelial detachment in 17 eyes (81.0%). Sustained improvement in visual acuity was obtained in seven eyes (33.3%), and stabilization of visual acuity in one eye. Analysis of available data describing the natural history of this condition indicates that although photocoagulation does not reduce the incidence of choroidal neovascularization, the treatment can be beneficial.     

Pars plana vitrectomy for regression of choroidal neovascularization with age-related macular degeneration

OBJECTIVE: In age-related macular degeneration, the posterior vitreous surface often remains attached to a higher degree than expected for the patient's age, suggesting the involvement of the posterior vitreous membrane in the pathophysiology of choroidal neovascularization. Thus, we performed simple pars plana vitrectomy and artificial posterior vitreous detachment in order to induce regression of choroidal neovascularization. METHODS: Vitrectomy was performed in 12 eyes of 11 patients with age-related macular degeneration in whom the posterior vitreous surface remained attached, and in whom there was evidence of highly active choroidal neovascularization. The posterior vitreous membrane was artificially detached during surgery, but photocoagulation and/or a subretinal procedure for choroidal neovascularization was not performed. Patients underwent fluorescein and indocyanine green angiography both pre- and postoperatively to assess the status of choroidal neovascularization. RESULTS: Six months after surgery, 6 of the 12 eyes showed regression of choroidal neovascularization, and in 2 eyes it had disappeared completely. Subretinal exudative changes in 8 eyes had improved. Visual acuity testing showed improved vision in 4 eyes, unchanged vision in 4 eyes, and worsening of vision in 4 eyes. The final best corrected visual acuity was 10/20 or better in one eye, 10/ 20 to 20/200 in 7 eyes, and 20/200 or worse in 4 eyes. CONCLUSION: The results of the present study suggest the involvement of the posterior vitreous membrane in the pathophysiology of age-related macular degeneration. Furthermore, the minimally invasive pars plana vitrectomy may represent a new treatment for age-related macular degeneration.     

Natural history of retinal pigment epithelial detachments in age-related macular degeneration

The natural history of 100 eyes of 93 patients with retinal pigment epithelial detachment (PED) and bilateral age-related macular degeneration (AMD) was retrospectively studied for a minimum of 12 months in the offices of Retina Consultants, Ltd. Detachment was defined as serous in 46 eyes, turbid in 12 eyes, hemorrhagic without evident neovascular membrane (NVM) in 20 eyes, and hemorrhagic with angiographically proven NVM in 17 eyes. Final visual results demonstrated visual acuity of 20/200 or worse in 33% of serous PED, 83% of turbid PED, and 89% of hemorrhagic PED. Despite strict inclusion criteria, 26% of serous PED developed NVM by one year and 49% of serous PED developed NVM by three years. Variables associated with NVM development in serous PED include older patient age, larger detachment size, presence of subretinal fluid at initial examination, and disciform scar in the fellow eye at presentation.     

Macular translocation for subfoveal choroidal neovascularization in age-related macular degeneration: a prospective study.

PURPOSE: To conduct a prospective study of macular translocation in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. METHODS: In 10 eyes of 10 patients with subfoveal choroidal neovascularization and best-corrected visual acuity ranging from 20/50 to 20/800 (median, 20/111), the fovea was relocated by means of scleral imbrication, intentional retinal detachment with small posterior retinotomies, and partial fluid-air exchange. In two eyes, the choroidal neovascular membranes were removed at the time of macular translocation; in seven eyes they were photocoagulated in the postoperative period; and in one eye the membrane was removed during reoperation to unfold a macular fold. RESULTS: All 10 eyes were followed up for 6 months. The median postoperative foveal displacement was 1286 microm (range, 114 to 1,919 microm). In three eyes (30%), a foveal fold formed postoperatively requiring reoperation, with one of these eyes requiring a second reoperation for a rhegmatogenous retinal detachment. Best-corrected visual acuity improved in four eyes (median, 10.5 letters) and decreased in six eyes (median, 14.5 letters). The median change in visual acuity was a decrease of 5 letters. The final best-corrected visual acuity was 20/80 in two eyes, 20/126 in one eye, 20/160 in four eyes, 20/200 in one eye, 20/250 in one eye, and 20/640 in one eye. CONCLUSIONS: Our initial experience with limited macular translocation suggests that this surgical technique is unpredictable. However, in patients with subfoveal choroidal neovascularization from age-related macular degeneration, it offers the potential for improving visual function and may be associated with less loss of vision than the disease itself, if allowed to progress. Further refinements in surgical indications and technique are needed to make this procedure safer, more predictable, and more beneficial.     

Hyperfluorescence associated with serous retinal pigment epithelial detachment on indocyanine green angiography

PURPOSE: Indocyanine green angiography has been reported to improve detection and delineation of occult choroidal neovascularisation in serous pigment epithelium detachment in age-related macular degeneration. The study aims to evaluate the visual acuity results of eyes affected by serous pigment epithelium detachment in age-related macular degeneration, having had indocyanine green-directed laser photocoagulation, and to correlate them to the pattern of serous pigment epithelium detachment on indocyanine green angiography. METHODS: Thirty-four eyes of 31 patients affected by serous pigment epithelium detachment in age-related macular degeneration were prospectively considered. Each patient underwent an ophthalmological examination including fluorescein and indocyanine green angiography one day before, and 6 weeks, 3 months, 6 months, 9 months, 12 months and 24 months after krypton-laser treatment. The serous pigment epithelium detachment was classified in the late-phases angiograms as either hypofluorescent, isofluorescent or hyperfluorescent comparing the fluorescence of the serous pigment epithelium detachment with the choroidal background fluorescence. RESULTS: The indocyanine green-guided laser treatment was associated with a temporary stabilization and a long-term progressive reduction of visual acuity: after 24 months visual acuity improved in 2.9%, stabilized in 26.5% and worsened in 70.5% of cases. Serous pigment epithelium detachment presenting a pretreatment hyperfluorescence had a final visual acuity of 0.06, with subfoveal choroidal neovascularisation development in 100% of cases, whereas serous pigment epithelium detachment presenting a pretreatment hypofluorescence and isofluorescence showed a final visual acuity of 0.12, with subfoveal choroidal neovascularisation development in 43.5% of eyes, with statistically significant difference. CONCLUSION: Overall visual acuity decreases with time after indocyanine green-guided laser treatment of choroidal neovascularisation in serous pigment epithelium detachment, and serous pigment epithelium detachment becoming hyperfluorescent in the late-phases of indocyanine green angiography has the worst functional outcome.     

45岁以上黄斑区神经上皮脱离患者疾病类型分析

目的 观察45岁以上患者发生黄斑区浆液性神经上皮脱离的疾病类型,探讨疾病诊断必要的辅助检查方法.方法 对年龄在45岁以上,双目间接检眼镜检查结合光相十断层扫描(OCT)确诊为黄斑区浆液性神经上皮脱离患者46例49只眼的临床资料进行同顾性分析.所有患者均接受荧光素眼底血管造影(FFA)、吲哚青绿血管造影(ICGA)检查.结合 FFA、ICGA和OCT检查做出诊断.结果 中心性浆液性脉络膜视网膜病变(CSC)31例34只眼,占所有患者的69.4%.其中,9例12只眼呈典型CSC表现,占CSC患者的35.3%;22例22只眼为慢性CSC,占CSC患者的64.7%.渗出型老年性黄斑变性(AMD)12例12只眼,占所有患者的24.5%.其中隐匿型9例,占AMD患者的75%;轻微经典型2例,占16.7%;经典型1例,占8.3%.息肉样脉络膜血管病变(PCV)3例3只眼,占6.1%.结论 45岁以上患者发生单纯黄斑区浆液性神经上皮脱离病因复杂,ICGA检查对慢性CSC、隐匿型CNV和PCV鉴别诊断有一定的作用.     

Comparison of fluorescein angiography and indocyanine green angiography for imaging of choroidal neovascularization in hemorrhagic age-related macular degeneration

PURPOSE: To compare fluorescein angiography and indocyanine green angiography for imaging of choroidal neovascularization located under subretinal hemorrhage, in age-related macular degeneration. METHODS: In a retrospective study, 30 eyes of 30 consecutive patients with hemorrhagic age-related macular degeneration were evaluated with fluorescein angiography and indocyanine green angiography. In each eye, areas of macular hemorrhage, choroidal neovascularization, and total lesion (hemorrhage plus choroidal neovascularization) were measured, and the choroidal neovascularization was categorized as classic, occult, or mixed on fluorescein angiography, and as hot spot, plaque, or combined lesion on indocyanine green angiography. Results of the two techniques were compared for the ability to identify a laser-treatable lesion. RESULTS: Fluorescein angiography showed fluorescence in most cases (28, 93.3%). In 23 cases (76.6%), the fluorescence pattern was compatible with occult choroidal neovascularization. Indocyanine green angiography revealed defined patterns of fluorescence in 27 cases (90%): 12 hot spots, seven plaques, and eight combined hot spots and plaques. Twenty lesions (66.6%) detected by indocyanine green angiography were considered eligible for laser therapy. Nine of them (45%) were extrafoveal. CONCLUSIONS: Indocyanine green angiography is beneficial for imaging choroidal neovascularization located under subretinal hemorrhage. Choroidal neovascularization demonstrated on indocyanine green angiography may be considered eligible for laser treatment. Therefore, indocyanine green angiography should be considered in cases of hemorrhagic age-related macular degeneration.     

Optical coherence tomography in the assessment of retinal pigment epithelial tear

PURPOSE: To study the findings of optical coherence tomography (OCT) in retinal pigment epithelial (RPE) tears. METHODS: Sixteen eyes of 16 consecutive patients with age-related macular degeneration complicated by RPE tear were studied using OCT. Fluorescein angiography also was performed. Thirteen eyes were at the acute stage and three eyes were at the scarring stage, still with a recognizable tear. RESULTS: Optical coherence tomography identified an RPE detachment (PED) with focal interruption of the RPE in all cases. Optical coherence tomography always highlighted a peculiar non-dome-shaped profile of the serous PED, as opposed to that of the PED not complicated by an RPE tear. A very intense hyperreflectivity was observed in the OCT scans performed through the retracted RPE. A deep hyperreflectivity under the line corresponding to the RPE was evident in the area of the bare choroid. No choroidal neovascularization could be visualized using OCT, either at the acute or at the scarring stages. CONCLUSIONS: Optical coherence tomography, a noncontact, noninvasive imaging technique, may be a useful tool, complementary to fluorescein angiography, in the clinical assessment of RPE tears.     

Peripheral retinal detachments and retinal pigment epithelial atrophic tracts secondary to central serous pigment epitheliopathy

Twenty-five patients with central serous pigment epitheliopathy (CSP), also known as central serous chorioretinopathy, have been observed to have inferior hemispheric retinal pigment epithelial atrophic tracts, presumptive of antecedent retinal detachments. Five of these patients were noted to have clinically discernible, dependent peripheral retinal detachments. The clinical and fluorescein angiographic features of these patients are reviewed. Alterations in the retina, the retinal pigment epithelium (RPE) and the choroid are also described. They include the commonly associated manifestations of CSP such as RPE leaks and macular detachment as well as some newly recognized disturbances such as retinal capillary dilatation (telangiectasia), retinal capillary leakage, retinal lipid deposition, cystoid macular edema, choriocapillaris atrophy, choroidal neovascularization and disciform scarring.     

Peripheral retinal detachments and retinal pigment epithelial atrophic tracts secondary to central serous pigment epitheliopathy. 1984

Twenty-five patients with central serous pigment epitheliopathy (CSP), also known as central serous chorioretinopathy, have been observed to have inferior hemispheric retinal pigment epithelial atrophic tracts, presumptive of antecedent retinal detachments. Five of these patients were noted to have clinically discernible, dependent peripheral retinal detachments. The clinical and fluorescein angiographic features of these patients are reviewed. Alterations in the retina, the retinal pigment epithelium (RPE) and the choroid are also described. They include the commonly associated manifestations of CSP such as RPE leaks and macular detachment as well as some newly recognized disturbances such as retinal capillary dilatation (telangiectasia), retinal capillary leakage, retinal lipid deposition, cystoid macular edema, choriocapillaris atrophy, choroidal neovascularization and disciform scarring.     

Evaluation of focal choroidal excavation in the macula using swept-source optical coherence tomography

Purpose

To evaluate imaging findings of patients with focal choroidal excavation (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and correlate it clinically.

Methods

Prospective observational case series. Eleven consecutive patients (12 eyes) with FCE were described. Data on demographics and clinical presentation were collected and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and SS-OCT) were analyzed.

Results

The primary diagnosis was epiretinal membrane (two eyes), choroidal neovascularization (one eye), polypoidal choroidal vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were conforming. One presented with a non-conforming lesion that progressed to a conforming lesion. One eye had multiFCE and two had two overlapping choroidal excavations. Using the SS-OCT, we found the choroid to be thinned out at the area of FCE but sclera remained normal. The choroidal tissue beneath the FCE was abnormal, with high internal reflectivity and poor visualization of choroidal vessels. There was loss of contour of the outer choroidal boundary that appeared to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was noted beneath this choroidal tissue and the choroidal–scleral interface was smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation to be stable in size.

Conclusion

FCE can be associated with epiretinal membrane, central serous chorioretinopathy, and age-related macular degeneration. The choroid was thinned out in the area of FCE.