Retinal angiomatous proliferation in age­related macular degeneration. 2001.

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 retinal­choroidal 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 retinal­retinal 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.

Fluorescein angiography: insight and serendipity a half century ago.

It has been 50 years since fluorescein angiography was developed as a clinical procedure by 2 medical students at Indiana University. The story of its discovery and the recognition of its value to ophthalmology involve a combination of insight and serendipity. Fluorescein had been in use clinically for more than half a century, but it took a pulmonary medicine laboratory to provide the stimulus for the development of flash and barrier filters that would make vascular photography practical. The first article was rejected by the ophthalmology literature, but several clinics heard about it and soon documented the enormous diagnostic value of the procedure.

The historical discovery of macular edema.

The occurrence of macular edema, or of intraretinal fluid in general, was largely unknown prior to the invention of the ophthalmoscope. One of the first reports on 'Retinitis in Glycosuria', a disease complex, which today would partly be described as diabetic maculopathy, was published in 1856 by Jaeger. His observations were confirmed less than twenty years later by Nettleship in London, and in 1875 Appolinaire Bouchardat from Paris described fluid and lipid accumulation in the macula which led--in his words--to a glucose induced amblyopia. The first pathophysiological hypotheses of fluid accumulation in the posterior pole were then put forward in 1882 by Tartuferi, who thought the edema represented swelling of photoreceptor sheaths. In 1896, the Frenchman Nuel coined the term 'oedème maculaire' which he had observed in a retinitis pigmentosa patient. However, it was not until the end of the first World War, that the Swiss ophthalmologist Alfred Vogt observed macular edema in a variety of other ocular conditions such as iridocyclitiOFF macular edema to a macular hole. A quarter of a century later Bangerter coined the German term 'Zystoides Makulaödem', and in 1950, Hruby was the first to draw attention to the development of macular edema after cataract extraction. Three years later this was followed by Irvine's classical paper on cystoid macular edema after intra- and extracapsular cataract extraction which had been complicated by incarceration of the vitreous in the anterior segment with consecutive tugging on the macula. A decade later, the phenomenon of cystic fluid accumulation in the macula after cataract extraction was further characterised by Gass and Norton using fluorescein angiography. The ensuing years saw the emergence of new concepts regarding the blood-retinal barrier and the paramount role of its dysfunction in the development of macular edema.