A previous study of 150 patients by Pauliekhoff et al
showed that fellow eyes of subjects with serous pigment epithelial detachments had larger, more densely packed, and less fluorescent drusen suggesting that the characteristics of the drusen were important predictors for wet AMD.10
At the time of publication of that report, the subclassification of CNV types into the currently accepted categories had not yet been developed. More recently, the nomenclature has evolved for the classification of CNV subtypes,11,12
and methods have been developed to assess severity and extent of ARM features.2,3
In the Rotterdam Study, incidence and progression rates of ARM in the more severely affected eye were determined by stratification of ARM features to one of four exclusive stages at baseline and at follow up.3
This staging system was based on previous findings14–17
and assumed that more extensive macular changes would be associated with a higher risk of development of AMD with each successive stage of early ARM. The Rotterdam Study found that progression of early ARM stages to a more advanced stage occurred in a distinct pattern at a stable rate providing support for their model. We therefore used this method to stage the severity of ARM in the fellow eyes of our cohort. We also classified CNV in the first eye using the definitions developed in multiple clinical trials.11,12
Using the Rotterdam severity stages and MPS definitions we have shown that a clear relation exists between increasing severity of ARM characteristics in the fellow eye with increasing proportion of occult disease in the first eye. Conversely, the fellow eyes of subjects with predominantly or wholly classic CNV in the first eye tended exhibited less severe stages of ARM.
Pauleikhoff et al10
subdivided their study cohort into five groups—namely, (1) serous pigment epithelial detachments, (2) neovascular RPE detachments, (3) well defined subretinal vascular complexes, (4) early ill defined hyperfluorescence, and (5) late ill defined hyperfluorescence. Group 3 of Pauleikhoff’s study corresponds to the classic CNV subgroup in the present study. It was therefore noteworthy that Pauleikhoff et al
found significantly larger and more densely packed drusen in their group 2 eyes in comparison with their group 3 eyes. Thus, the findings of the present study not only support those of Pauleikhoff et al
but also suggest that occult CNV is associated with widespread RPE dysfunction whereas classic CNV may be the consequence of a more focal breakdown of the barrier between the retina and the choroid. As many pathogenetic studies implicate drusen, pigmentation, and RPE atrophy in RPE dysfunction16–23
our findings are consistent with the body of evidence that supports the view that drusen develop as a consequence of overloading and failure of the RPE over a long period of time.
Our findings also imply that classic and occult CNV occur as a result of distinct pathological processes, albeit sometimes in the same eye at adjacent locations and concur with the observations of several investigators10,24
that changes in Bruch’s membrane that induce exudative lesions should not be regarded as a single process.
Our hypothesis is also consistent with clinical findings that have been observed in many studies for which sound scientific explanations have not been forthcoming. For example classic and occult CNV respond differently to treatment by argon laser, with the former being easily ablated in its entirety, whereas treatment of the latter by argon laser simply results in the expansion of the lesion.13,22,23
More recently, clinical trials have shown a strong beneficial effect of verteporfin PDT in eyes with wholly classic or predominantly classic CNV with no effect on eyes with minimally classic CNV (TAP and VIP trials).12,25
Finally, the largest cohort study of eyes without CNV at baseline (study of fellow eyes enrolled into the MPS juxtafoveal and subfoveal trials) has shown that even those free of large drusen and hyperpigmentation have a 10% chance of developing CNV over a 5 year period indicating that the risk is not negligible.15,26
The present study which was cross sectional was not designed to answer the question whether the morphological composition of the CNV in the first eye influenced the rate of development of CNV in fellow eyes. The MPS study on the 5 year follow up of fellow eyes without neovascular AMD at baseline did not find a difference in risk of neovascularisation when subjects were characterised by the type of CNV in the first eye.22
None the less, as the present study has demonstrated a dose relation between the proportion of occult CNV in the first eye and the severity of ARM in the fellow eye there would appear to be a strong scientific rationale for examining the relation between the extent of occult CNV and risk of neovascularisation in the fellow eye.
Although we found no association between the severity of ARM in the fellow eye with smoking status, sex, or history of cardiovascular problems, the present study had limited numbers and hence limited power to identify contributions from systemic factors.
It is also limited by its cross sectional approach and its retrospective nature. None the less, our findings suggest that the health of the RPE is compromised in the fellow eyes of patients with occult CNV in the first eye and may be an important pathogenetic factor. Our data suggest that multiple pathogenetic mechanisms operating in tandem determine whether an eye will develop classic or occult CNV and which subtype will predominate. This hypothesis could be tested by longitudinal studies of fellow eyes of subjects with unilateral CNV utilising the newer technologies that can image the RPE choroidal interface with precision. The results of the present study provide clues for improved prognostic indicators and may help in designing protocols to evaluate the risk of developing CNV in the fellow eye.