High-risk characteristics of fellow eyes of patients with unilateral neovascular age-related macular degeneration

doi:10.1016/S0161-6420(98)93025-1

Ophthalmology

Volume 105, Issue 3, 1 March 1998, Pages 441-447

https://doi.org/10.1016/S0161-6420(98)93025-1 Get rights and content

Abstract

Objective

This study aimed to determine whether clinical tests of ocular function and macular appearance independently can help to predict which patients with unilateral neovascular age-related macular degeneration (AMD) will have a choroidal neovascular membrane (CNVM) develop in their fellow eye.

Design

The study design was a prospective cohort study.

Participants

One hundred twenty-seven patients with unilateral neovascular AMD observed for up to 4.5 years participated.

Intervention

Functional measurements included visual acuity, macular visual field, glare recovery time, and foveal electroretinogram amplitude and implicit time.

Main outcome measure

The age-adjusted proportion of patients having a CNVM develop over follow-up assessed by the Cox proportional hazards model with stepwise selection was measured.

Results

On average, 8.8% of patients had a CNVM develop each year. Independent risk factors for the fellow eye were its glare recovery time in minutes (relative risk = 1.30, confidence interval = 1.10–1.54, P = 0.003) and its extent of visible macular abnormalities on a four-point scale (relative risk = 1.62, confidence interval = 1.06– 2.59, P = 0.03). Of the fellow eyes that converted, the interval to have a CNVM develop was inversely related to the foveal electroretinogram implicit time.

Conclusions

A slower recovery from glare and more extensive funduscopic changes appear to be independent risk factors for the development of a CNVM in the fellow eyes of patients with unilateral neovascular AMD. A slower foveal electroretinogram implicit time may be a sign of early stage CNVM development, perhaps because of outer retinal ischemia. These results have clinical management implications, particularly for those patients at high risk of having a potentially treatable form of AMD develop.

Section snippets

Enrollment

Patients with unilateral neovascular AMD were identified by referral from ophthalmologists in New England (87% of cases) or by self-referral in response to advertisement (13% of cases). Patients were informed that they would receive a screening-baseline examination and, if eligible, be asked to return for re-examination every 6 months thereafter for at least 3 years. Eligibility criteria were a corrected Snellen visual acuity of 20/ 60 or better in the fellow eye with sufficiently clear media

Overall rate of having a choroidal neovascular membrane develop

Table 1 lists by follow-up visit the cumulative proportion of patients who failed (i.e., in whom a CNVM developed), the number of patients who failed, the number of patients who were censored for the next visit (i.e., those subsequently lost to follow-up), and the number of at-risk patients (i.e., those who had not failed at a previous visit or been lost to follow-up). The table reflects that 19 patients (15%) were lost to follow-up by the third year; this number includes 14 who died. Based on

Discussion

The annual rate of having a CNVM develop in the fellow eye of patients with unilateral neovascular AMD studied for up to 4.5 years was 8.8% in the current prospective study, slightly higher than that (6%) found in a previous prospective study that observed patients for 5 years.10 Both rates of conversion lie within the range of rates reported by several retrospective studies.4, 5, 6, 7, 8, 9

We identified two independent, age-adjusted baseline predictors of choroidal neovascularization in the

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Cited by (49)

Six-Year Incidence of Age-Related Macular Degeneration in Asian Malays: The Singapore Malay Eye Study
2017, Ophthalmology
Citation Excerpt :
In the current study, although the number of participants with unilateral late AMD at baseline was only 4, 50% of this group demonstrated late AMD in the second eye over 6 years. This finding is compatible with the findings of previous reports.32–35 Strengths of the current study include the adoption of methodology and grading almost identical to those used in the landmark BDES and BMES.
To determine the 6-year incidence of early and late age-related macular degeneration (AMD) in a Singaporean Malay population and to validate the Age-Related Eye Disease Study (AREDS) simplified severity scale in Asians.
Prospective, population cohort study.
The Singapore Malay Eye Study baseline participants (age, ≥40 years; 2006–2008) were followed up in 2011 through 2013, and 1901 of 3280 of eligible participants (72.1%) took part.
Fundus photographs were graded using the Wisconsin AMD grading system.
Incidence of early and late AMD.
Gradable fundus photographs were available for 1809 participants who attended both baseline and 6-year follow-up examinations. The age-standardized incidences of early and late AMD were 5.89% (95% confidence interval [CI], 4.81–7.16) and 0.76% (95% CI, 0.42–1.29), respectively. The 5-year age-standardized incidence of early AMD (calculated based on the 6-year incidence) was lower in our population (5.58%; 95% CI, 4.43–7.01) compared with the Beaver Dam Eye Study population (8.19%). The incidence of late AMD in our population was similar to that of the Beaver Dam Eye Study population (0.98% [95% CI, 0.49–1.86] vs. 0.91%), the Blue Mountains Eye Study population (1.10% [95% CI, 0.52–9.56] vs. 1.10%), and the Hisayama Study population (1.09% [95% CI, 0.54–4.25] vs. 0.84%). The incidence of late AMD increased markedly with increasing baseline AREDS score (step 0, 0.23%; step 4, 9.09%).
This study documented the incidence of early and late AMD in a Malay population. The AREDS simplified severity scale is useful in predicting the risk of late AMD development in Asians.
Association of ARMS2 genotype with bilateral involvement of exudative age-related macular degeneration
2012, American Journal of Ophthalmology
To study the association of ARMS2 A69S genotype with the development of exudative age-related macular degeneration (AMD) in the unaffected fellow eye and to estimate the duration until the development of AMD in the second eye.
Retrospective cohort study.
We retrospectively reviewed 326 patients who had exudative AMD in at least 1 eye, genotyping of ARMS2 A69S, and a minimum follow-up of 2 years. Survival analysis and Cox proportional hazard regression analysis were used to examine the association between candidate factors and the duration until the development of AMD in the second eye.
One hundred nineteen patients (36.5%) had bilateral exudative AMD at the initial visit. A risk allele of ARMS2 A69S was more frequently seen in patients with bilateral AMD (P = .0270) than in those with unilateral AMD. Of the 207 unilateral AMD patients, 23 (11.1%) had AMD in the fellow eye after a mean duration of 56.3 ± 40.4 months. Fellow-eye involvement was associated with ARMS2 A69S genotype (hazard ratio [HR], 2.673; P = .0013), age (HR, 1.102; P = .0005), and smoking history (HR, 0.680; P = .3663). As HRs indicate, correlation of genotype (2.673) was as high as that of 10-year aging (1.102¹⁰ = 2.641). Survival analysis revealed that patients with risk homozygous (TT) genotype had second-eye involvement significantly earlier than those with other genotypes (P = .0028). When the observation duration reached 120 months, second-eye involvement had developed in 50%, 6.6%, and 11.2% of the TT, GT, and GG cohorts, respectively.
ARMS2 A69S genotype is associated with second-eye involvement of exudative AMD and with the period between first- and second-eye involvements.
Psychophysical Function in Age-related Maculopathy
2009, Survey of Ophthalmology
Citation Excerpt :
A delay in the PSRT was observed in 62% of patients, and was increased up to six times the upper limit of normal, suggesting that this test may be of prognostic value for CNV development. Furthermore, the same investigators, in a subsequent longitudinal study, demonstrated that a slow PSRT is an independent risk factor for developing CNV in the fellow eyes of patients with unilateral CNV, and the risk increases by a factor of 30% for each minute of delay in the PSRT.268 Interestingly, Collin et al have observed a relatively greater degree of PSRT prolongation in ARM patients with reduced VA when compared with ARM patients with normal VA (the authors described these patients as pre ARM patients).70
Age-related macular degeneration (AMD), the late stage of age-related maculopathy (ARM), is the leading cause of blind registration in developed countries. The visual loss in AMD occurs due to dysfunction and death of photoreceptors (rods and cones) secondary to an atrophic or a neovascular event. The psychophysical tests of vision, which depend on the functional status of the photoreceptors, may detect subtle alterations in the macula before morphological fundus changes are apparent ophthalmoscopically, and before traditional measures of visual acuity exhibit deterioration, and may be a useful tool for assessing and monitoring patients with ARM. Furthermore, worsening of these visual functions over time may reflect disease progression, and some of these, alone or in combination with other parameters, may act as a prognostic indicator for identifying eyes at risk for developing neovascular AMD. Lastly, psychophysical tests often correlate with subjective and relatively undefined symptoms in patients with early ARM, and may reflect limitation of daily activities for ARM patients. However, clinical studies investigating psychophysical function have largely been cross-sectional in nature, with small sample sizes, and lack consistency in terms of the grading and classification of ARM. This article aims to comprehensively review the literature germane to psychophysical tests in ARM, and to furnish the reader with an insight into this complex area of research.
Development of Typical Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Fellow Eyes of Japanese Patients with Exudative Age-related Macular Degeneration
2008, American Journal of Ophthalmology
Citation Excerpt :
According to the analysis in this study, typical AMD and PCV have very similar probabilities for the fellow eye to become involved in unilaterally affected Japanese patients and the cumulative incidence was about 11% over five years. In order to assess the potential to develop exudative AMD in fellow eyes, that drusen is a paramount precursor has been well documented in literature.1,7,18–20 In Asian populations (including both Japanese and Chinese), the prevalence of drusen is not as common as in patients.5,16,21
To investigate the development of typical age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) in fellow eyes of Japanese patients with exudative AMD.
Retrospective observational consecutive case series.
Two hundred and sixteen Japanese patients were enrolled in this study from the outpatient clinic of the University of Tokyo Hospital. Ninety-one patients had typical AMD and one hundred and twenty-five patients had PCV. The average follow-up period was 33.6 and 25.1 months for typical AMD and PCV patients.
The cumulative incidence of involvement in fellow eyes with overall exudative AMD, including both typical AMD and PCV, was 3.4% in one year, 9.3% in three years, and 11.3% in five years. It was 3.6%, 7.3%, and 11.2% in typical AMD, and 3.2%, 11.1%, and 11.1% in PCV in one, three, and five years, respectively. Before the development of exudative AMD, patients with typical AMD had a variety of funduscopic findings including retinal pigment epithelium (RPE) atrophy, drusen, drusenoid pigment epithelial detachments (PED), and normal macula. PCV patients, on the other hand, had funduscopic findings of RPE atrophy. Inner choroidal vascular abnormality of vascular network and polypoidal formation was observed in several eyes before the clinical manifestation of exudative changes.
Typical AMD and PCV had similar probabilities of involving the fellow eye in unilaterally affected Japanese patients. RPE atrophy was a prevailing finding in fellow eyes of patients who developed PCV. In PCV, choroidal vascular network and polypoidal formation gradually grow before exudative changes.
The Natural History and Prognosis of Neovascular Age-Related Macular Degeneration. A Systematic Review of the Literature and Meta-analysis
2008, Ophthalmology
Citation Excerpt :
The mean patient age was 74 years (range, 67–80), and 57.5% were female. The mean time from diagnosis to study commencement was 16 months in the 4 studies reporting this outcome.20,39,48,53 In studies that reported whether the disease was present in both eyes (27), 72.4% of the patients had unilateral choroidal neovascularization.
To describe the natural history and progression of visual loss in eyes with untreated neovascular age-related macular degeneration (AMD).
Systematic review and meta-analysis.
Four thousand three hundred sixty-two untreated neovascular AMD patients from published interventional studies.
A systematic review of the literature from 1980 to August 2005 was performed. Studies reporting disease progression outcomes for untreated patients with neovascular AMD were included. Outcome measures were summarized using simple counts and means. Random effects meta-analyses were conducted and tests of heterogeneity were performed where appropriate.
Changes in visual acuity (VA) loss, development of comorbidities, and fellow eye involvement.
Fifty-three primary studies were included. Nearly half of the studies (28) were randomized clinical trials. The quality of the studies was high, with over 80% providing level I or II evidence. Mean baseline VA among study patients was 0.64 logarithm of the minimum angle of resolution (logMAR) (∼20/87 Snellen). The mean VA change in logMAR progressed from 0.1 (1 line lost) at 3 months to 0.3 (2.7 lines lost) after 12 months and 0.4 (4 lines lost) after 24 months. The proportion of patients who developed severe vision loss (>6 lines) from baseline increased from 21.3% at 6 months to 41.9% by 3 years. The proportion of patients with VA worse than logMAR 1.0 (20/200 Snellen) increased from 19.7% at baseline to 75.7% by 3 years. Neovascular AMD developed in the fellow eye in 12.2% of patients by 12 months and in 26.8% by 4 years. Meta-analyses of vision outcome by subtype of neovascular AMD were not possible.
A doubling of the visual angle of presenting VA may be expected to occur in the year after initial presentation in eyes with untreated neovascular AMD. No conclusions can be drawn as to the differences in rates of disease progression by neovascular AMD subtype. The diversity of reporting formats, paucity of long-term natural history data, and heterogeneity among the reported clinical studies impose limits to the clear understanding of long-term prognosis for visual function in neovascular AMD.
Two genetic pathways for age-related macular degeneration
2007, Current Opinion in Genetics and Development
Citation Excerpt :
In further support of this observation, allele frequency estimates of the CFH 402H risk allele are significantly higher in Caucasians than in Asians (>35% versus <5%, respectively) [20–22]. In Asian populations, uncontrolled accumulation of soft drusen is rarely observed [23–25]; thus, the low rate of soft drusen accumulation in Asians is a likely consequence of the reduced frequency of the CFH 402H risk allele. Subsequent screening of complement pathway components has identified additional variants of complement factor B (CFB) that, along with CFH 402H, increase the risk of AMD beyond that conferred by the CFH variant alone [26••].
The discovery of strong associations of the His402 variant of complement factor H (CFH) and the change in the promoter region of HtrA serine peptidase 1 (HTRA1) with age-related macular degeneration (AMD) have altered our conception of the pathophysiology of this disease. The complement system has been placed at the center of a flurry of research interest, and a similar growth in attention to the serine proteases is not far behind. The specific role of these variants in causing AMD is unknown, but they will undoubtedly lead to a deeper understanding of the biological mechanisms and will point to new avenues for pharmacologic management. Furthermore, these variants will enable clinicians and investigators to identify people at high risk for this condition, thereby establishing the preconditions for preventing the disease.

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^☆: Supported by grants from the National Eye Institute (EY08398), the Foundation Fighting Blindness, Baltimore, Maryland, and the Massachusetts Lions Eye Research Fund, Inc.

¹: The authors have no proprietary interest in the products described in this article.

²: Asher Weiner currently is affiliated with the Division of Ophthalmology, Columbia-St. Luke’s Medical Center, Cleveland, Ohio.

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High-risk characteristics of fellow eyes of patients with unilateral neovascular age-related macular degeneration1☆,

Abstract

Objective

Design

Participants

Intervention

Main outcome measure

Results

Conclusions

Section snippets

Enrollment

Overall rate of having a choroidal neovascular membrane develop

Discussion

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Am J Ophthalmol

Vision Res

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Int Ophthalmol

Age-related macular degenerationepidemiology

Age-related macular degeneration and blindness due to neovascular maculopathy

Arch Ophthalmol

High-risk characteristics of fellow eyes of patients with unilateral neovascular age-related macular degeneration¹☆,