How Prevalent is Macular Telangiectasia Type 2?

Sallo and co-investigators report in this issue of the journal the results of two African population-based studies on the prevalence of macular telangiectasia type 2, an acquired form of an ocular condition known previously as juxtafoveal or perifoveal telangiectasia.¹ This ocular condition of unknown etiology is characterized by vascular abnormalities and neurodegeneration. Prior evaluations of its prevalence were conducted also in population-based cohorts of individuals of European descent in the US (Beaver Dam Eye Study²) and Australia (Melbourne Collaborative Cohort Study³). Such studies are important and complementary to the international research effort of the Macular Telangiectasia (MacTel) Project which has enrolled more than 500 participants.⁴ The goal of this research group which includes clinical sites in seven countries and basic scientists in various laboratories, is to evaluate possible etiology, natural history, and potential therapies of macular telangiectasia type 2.

The prevalence of macular telangiectasia type 2 in Africa is estimated by these investigators to be 0.06% (95% CI 0.02–0.21%) in Kenya, 0.06% (95% CI 0.01–0.17%) in Nigeria with a combined rate of 0.06% (95% CI 0.02–0.14%) in the two African study populations. The prevalence rate in the Melbourne Collaborative Cohort Study in Australia ranges from 0.0045–0.022%, while the Beaver Dam Eye Study in the US estimates the rate to be 0.1%, bracketing the rates found in Africa. No previous study has demonstrated any racial preferences. In order to understand the differences in these prevalence rates, we need to understand the disease state as well as the methodology used in these different population-based studies.

All studies of prevalence were conducted based upon analyses of fundus photographic gradings. There are challenges to the identification of macular telangiectasia type 2 by color fundus photographs as this disease begins, as noted by the investigators, with the graying or retinal opacification of the macular area which is difficult to capture on color fundus photography. Other clinical characteristics include the development of ectatic capillaries that start temporally and eventually encompass the fovea, demonstrated by marked leakage on fluorescein angiography. Crystalline deposits are seen at the vitreoretinal interface; blunted, dilated venules, that make right angle turns, dive into the deeper retinal layers; and intra-retinal pigment migration and retinal pigment epithelial hyperplasia along these diving dilated venules are characteristic lesions. These lesions appear in an orderly fashion along the natural history of the disease. In some eyes, neovascularization occurs. Many of these features are evident on color fundus photographs.

In addition, atrophic changes in the neurosensory retina are typically seen in the later stage of the disease. This is most easily detected on optical coherence tomography (OCT). In the natural course of macular telangiectasia type 2, OCT shows hyporeflective cavities in the inner retina and eventually hyporeflective cavities in the outer neurosensory retina involving the inner segment and outer segment junction. These lesions eventually lead to atrophy.

Another interesting characteristic is abnormal fundus autofluorescence. The MacTel Project investigators observed that one of the earliest signs of macular telangiectasia type 2 is the loss of the hypofluorescent center seen normally on fundus autofluorescence (blue-light), due to the loss of macular pigment in this condition. This can be present without any other abnormalities while the fellow eye may show typical lesions of macular telangiectasia type 2. Another characteristic finding is the presence of fluorescein leakage, beginning with the temporal macula to involving the entire fovea.⁵

Although most of the lesions of macular telangiectasia type 2 are readily documented on color fundus photography, the best modalities to diagnose this condition include fundus autofluorescence and OCT. Fluorescein angiography would be useful to evaluate the leaking ectatic vessels around the fovea and the neovascularization that develops in the late stages. Most population-based studies, however, do not include such measurements.

In these three studies, there was variation in the photographic techniques as well as the grading methodology that may account for the differences in the prevalence rates found in the three different continents. The Melbourne Collaborative Cohort Study was conducted using a nonstereoscopic non-mydriatic fundus camera of 45° while the Beaver Dam Eye Study used a stereoscopic fundus camera of 30°. The African studies were conducted using a digital non-mydriatic camera. Interestingly, both the African study as well as the Beaver Dam Eye Study graded each eye for the presence of macular telangiectasia type 2 while the Australian study only directly graded the eyes for macular telangiectasia type 2 if the previous grading detected a lesion that was characteristic for the condition. This may indeed account for the differences, and the inability of the fundus photographs to detect the early stages of the disease would also suggest that these prevalence figures have underestimated the true prevalence of this condition, possibly on all three continents.

Future population-based studies have incorporated some of the newer modalities of imaging, such as spectral domain OCT. This would help to further refine the prevalence of this somewhat rare condition. This may also allow for the analyses of associated medical conditions such as diabetes mellitus. This commonly associated comorbidity of this ocular condition has not been detected in the small numbers of cases in these current studies. It is possible that diabetes has not yet been diagnosed.

While the MacTel project will provide further information on natural history and associated risk factors, these complementary population-based prevalence studies will help give perspective as to the impact of macular telangiectasia type 2 in the general population globally. We hope to gain further knowledge of the possible etiology and potential therapies that may be available for patients who are affected with this condition. A great deal of work is currently underway to determine clinical outcome measurements that may be meaningful to incorporate in controlled clinical trials of therapies for this neurodegenerative disease. Lessons learned from this condition may well apply to other neurodegenerative diseases.

Declaration of interest: The authors declare no conflicts of interest.