Evidence-based recommendations for the diagnosis and treatment of neovascular glaucoma.

PURPOSE: To succinctly update information on the pathogenesis, etiology, diagnosis, and treatment of neovascular glaucoma based on a systematic review of available literature and to provide summary recommendations rated for their importance to clinical outcome. CLINICAL RELEVANCE: Neovascular glaucoma is a devastating ocular disease that often results in loss of vision. The current standard of care includes retinal ablation and control of increased intraocular pressure with medical and surgical therapy. LITERATURE REVIEW METHODOLOGY: The authors conducted a MEDLINE literature search of articles published in English from 1966 to the present. Each article reviewed was rated as to the strength of evidence it provided, and summary ratings for the strength of evidence supporting clinical recommendations were generated. RESULTS: Level A (most important to patient outcome) recommendations for the diagnosis of neovascular glaucoma include a high index of suspicion, a full ocular examination including undilated gonioscopy, and pupil examination. In regard to treatment, Level A recommendations include treatment of the underlying disease origin, complete panretinal photocoagulation (if retinal ischemia is a factor), and medical control of both elevated intraocular pressure and inflammation. Level B recommendations (moderately important to patient outcome) encompass glaucoma surgery to control intraocular pressure when medical therapy is unsuccessful, although the ideal surgical procedure is unknown. Currently, trabeculectomy with antimetabolite therapy, aqueous shunt implants, and diode laser cyclophotocoagulation are the preferred surgical treatment options. CONCLUSIONS: The current literature on neovascular glaucoma has few articles that provide strong evidence in support of therapy recommendations (level I). Future research studies are needed to address areas in which the current evidence is moderately strong (level II) or weak, consisting only of a consensus of expert opinion (level III). Whenever practicable, these studies should be prospective, randomized clinical trials.

Long-term follow-up of unoperated macular holes.

OBJECTIVE: To investigate the anatomic and visual acuity outcomes among patients with unoperated macular holes and at least 5 years of follow-up. DESIGN: Retrospective, noncomparative case series from an institutional practice setting. PARTICIPANTS: All patients with unoperated full-thickness macular holes evaluated at Bascom Palmer Eye Institute between January 1, 1968 and December 31, 1993 and observed for at least 5 years. METHODS: Demographic and clinical data were abstracted from patients' medical records and ophthalmologic photography records. For patients with bilateral macular holes, only one eye was included. MAIN OUTCOME MEASURES: Visual acuity and clinical features on initial examination, at 5 years, and at final follow-up. RESULTS: The study included 65 eyes of 65 patients with a median age of 65 years (range, 52-85 years) and a median follow-up of 9.3 years (range, 5-29 years). On initial examination at Bascom Palmer Eye Institute, the macular hole was stage 2 in 15 eyes (24%), stage 3 in 23 eyes (37%), and stage 4 in 25 eyes (40%). At final follow-up, the macular hole was stage 3 in 10 eyes (16%) and stage 4 in 53 eyes (84%). Visual acuity was 20/200 or worse in 35 eyes (54%) on initial examination, in 43 eyes (74%) at 5 years, and in 53 eyes (82%) at final follow-up. Poorer visual acuity on initial examination was a significant predictor of poorer final vision (P < 0.01). Other accompanying clinical features such as the presence of operculum, posterior vitreous detachment, and epiretinal membrane were not significantly associated with final vision. Throughout follow-up, there was a redistribution and reduced number of yellow nodular opacities at the level of the retinal pigment epithelium at the base of the macular holes and the development of retinal pigment epithelial atrophy around the macular holes. CONCLUSIONS: Long-term follow-up of unoperated macular holes demonstrates progression in hole size and stage, vision loss which generally stabilizes at the 20/200 to 20/400 level, a redistribution and reduced number of yellow nodular opacities at the level of the retinal pigment epithelium, and the development of retinal pigment epithelial atrophy surrounding the macular hole, resulting in a "bull's-eye" macular appearance.

Differentiation between presumed ocular histoplasmosis syndrome and multifocal choroiditis with panuveitis based on morphology of photographed fundus lesions and fluorescein angiography.

OBJECTIVE: To evaluate whether inactive cases of presumed ocular histoplasmosis syndrome (POHS) and multifocal choroiditis with panuveitis (MFC) can be differentiated from each other by their appearance on fundus photography and fluorescein angiography. METHODS: Two masked observers classified 50 patients' photographs (27 with fluorescein angiograms) as POHS, MFC, or "indeterminate." Twenty-five patients had known POHS and 25 had known MFC. Statistical analysis was performed to assess agreement and interrater reliability. RESULTS: Observer A classified 33 patients and was indeterminate on 17. Of the 33, he was correct on 26 (79% crude accuracy; kappa = 0.560; 95% confidence interval [CI], 0.286-0.834). Observer B classified 40 patients and was indeterminate on 10. Of the 40, he was correct on 33 (82% crude accuracy; kappa = 0.650; 95% CI, 0.422-0.878). Both observers ventured a diagnosis on 28 common patients. Of these, they selected the same diagnosis on 26 (93% crude agreement). When the 2 observers' diagnoses were compared and indeterminate patients were factored in, the kappa value was 0.408 (95% CI, 0.215-0.601). When the indeterminate patients are excluded, the kappa agreement increased to 0.825 (95% CI, 0.592-1). When pictures only were available, observer A and observer B kappa values against the gold standard were 0.625 (95% CI, 0.270-0.980) and 0.588 (95% CI, 0.235-0.940), respectively. The pictures-only kappa values for observer A vs observer B were 0.582 (95% CI, 0.316-0.848) with indeterminate patients factored in and 1.0 (95% CI, 1.0-1.0) when indeterminate patients were excluded. Pictures and fluorescein angiogram kappa values were 0.493 (95% CI, 0.076-0.909) for observer A and 0.706 (95% CI, 0.413-0.999) for observer B against the gold standard. For observer A vs observer B, the kappa value was 0.261 (95% CI, -0.002 to 0.524) with indeterminate patients factored in and 0.567 (95% CI, 0.032-1) excluding indeterminate patients. Sensitivity for all cases for observer A was 60% (+/-13%) for POHS and 94% (+/-6%) for MFC. For observer B, the sensitivity for all cases was 70% (+/-10%) for POHS and 95% (+/-5%) for MFC. CONCLUSIONS: Given adequate funduscopic information, the experienced observer can often accurately distinguish between POHS and MFC without the need for ancillary testing. Angiography in addition to fundus photography does not appear to increase diagnostic ability. There appears to be a higher sensitivity for MFC than for POHS.

Juxtapapillary capillary hemangiomas. Clinical features and visual acuity outcomes.

OBJECTIVE: To describe the clinical features, association with von Hippel-Lindau (VHL) disease and visual acuity outcomes of patients with a juxtapapillary capillary hemangioma. DESIGN: Retrospective observational case series. PARTICIPANTS: Seventy-two eyes of 68 patients identified with a juxtapapillary capillary hemangioma. Follow-up data of at least 6 months duration were available for 60 eyes. METHODS: A retrospective chart review of patients diagnosed with a juxtapapillary capillary hemangioma examined at four medical centers. MAIN OUTCOME MEASURES: Age at diagnosis, visual acuity (VA) at first examination and at last follow-up, tumor growth pattern and location, associated clinical features, type of treatment, association with VHL, and presence of peripheral hemangiomas were recorded for each patient. RESULTS: On initial examination, VA was >/=20/40 in 43 of 70 eyes (61%) and was >/=20/200 in 60 eyes (86%). At an average follow-up of 5.4 years (range, 0.5-19 years), VA of >/=20/40 was achieved in 21 eyes (35%) and >/=20/200 in 33 eyes (55%). Patients with VHL had poorer initial VA (48% vs. 70% with VA >/=20/40, and 74% vs. 93% with VA >/=20/200) and final VA (26% vs. 41% with VA >/=20/40, and 39% vs. 65% with VA >/=20/200) compared with patients without VHL. Patients with VHL more commonly were seen at an earlier age (average, 20 vs. 44 years, P: < 0.001), with bilateral (17% vs. 0%), and/or peripheral (39% vs. 0%) (P: < 0.001) tumors that more often had an endophytic growth pattern (63% vs. 22%, P: = 0.001) compared with patients without VHL. Patients selected for laser treatment generally had poorer initial (52% vs. 74% with VA >/=20/40, 79% vs. 96% with VA >/=20/200) and final VAs (18% vs. 56% with VA >/=20/40, 45% vs. 67% with VA >/=20/200) compared with patients not treated with laser. CONCLUSIONS: On long-term follow-up of patients with a juxtapapillary capillary hemangioma, the VA generally worsens. Patients with VHL and a juxtapapillary hemangioma more often present at a younger age, have tumors with an endophytic growth pattern, and have bilateral, multiple tumors. Treatment with laser photocoagulation results in variable VA outcomes.

Familial spastic paraplegia and maculopathy with juxtafoveolar retinal telangiectasis and subretinal neovascularization.

PURPOSE: To describe a previously unreported condition involving familial spastic paraplegia and a peculiar type of maculopathy. METHODS: Two pairs of siblings were studied. All four cases underwent serial clinical examinations, fundus photography, and fluorescein angiography. Two siblings had extensive investigations. RESULTS: Characteristics of the four cases include spastic paraplegia diagnosed in the first decade of life and visual loss at about age 9 due to a maculopathy with an abnormal vascular complex. In the early stages, parafoveal dilatation of the capillary network was noted. The later stages were characterized by cystic macular degeneration, and seven of eight eyes developed fibrovascular scars with retinochoroidal anastomoses, pigment migration, and atrophic changes. In two siblings, electro-oculographic findings were subnormal, whereas results of electroretinography, magnetic resonance imaging of the brain and spinal cord, and metabolic and karyotype studies were normal. These siblings were an Indonesian girl and boy; the other siblings were white males. There was no consanguinity of the parents and family history was unremarkable. CONCLUSIONS: This study suggests that the two pairs of siblings have an identical familial and probably recessive disorder with neurodegenerative changes that have caused paraplegia and a peculiar maculopathy associated with anomalous retinal vascular complexes, retinochoroidal anastomoses, and subretinal neovascularization.

Association of the apolipoprotein E gene with age-related macular degeneration: possible effect modification by family history, age, and gender.

PURPOSE: Age-related macular degeneration (AMD) is a complex disorder affecting older adults in which genetic factors are likely to play a role. It has been previously suggested that the e4 allele of the apolipoprotein E (APOE) gene may have a protective effect on AMD risk and that the e2 allele may increase disease risk. The purpose of our study was to examine whether an independent data set would support the proposed role of APOE in AMD etiology. METHODS: We compared AMD cases (n=230) to controls (n=372) with respect to APOE genotypes using c2 tests and logistic regression analysis. We also conducted separate analyses for familial (n=129) and sporadic (n=101) AMD cases since these groups may have a different disease etiology. RESULTS: We did not find evidence for the risk-increasing effect attributed to the e2 allele in either familial or sporadic AMD. No evidence for a protective effect of the e4 allele was obtained for sporadic AMD. The age- and sex-adjusted odds ratio (OR) for e4 carriers among familial AMD cases compared to controls was 0.66 (95% confidence interval: 0.38-1.12, p=0.13). In the subgroup of individuals younger than 70 years of age, an OR of 0.24 (95% confidence interval: 0.08-0.72, p=0.004) was obtained. CONCLUSIONS: Our data modestly support a protective effect of the APOE-e4 allele on AMD risk, but emphasize the need to investigate more thoroughly whether the effect could be restricted to cases with a family history of AMD and whether it varies across age and sex groups.

Diffuse bilateral subacute neuroretinitis: first patient with documented nematodes in both eyes.

OBJECTIVE: To describe the first patient with documented evidence of diffuse unilateral subacute neuroretinitis (DUSN) in both eyes. METHODS: A 10-year-old healthy Brazilian girl was first seen with signs of late-stage DUSN in both eyes. A careful search for a nematode was performed in each eye. RESULTS: A motile 550- to 660-microm nematode was found in the inferotemporal retina of the left eye. A similar-sized motile nematode was found in the superotemporal retina of the right eye. Both nematodes were treated with argon green laser applications with bilateral improvement of visual function. CONCLUSION: Although most patients with DUSN do not develop the disease in the fellow eye, this case demonstrates that DUSN can occasionally affect both eyes.

Focal retinal pigment epithelial dysplasia associated with fundus flavimaculatus.

BACKGROUND: One or more focal dysplastic lesions of the retinal pigment epithelium (RPE) occurred in 15 eyes of 10 patients with fundus flavimaculatus. METHODS: Review of patient records including an attempt to obtain follow-up information concerning a history of previous ocular trauma. RESULTS: Mild antecedent ocular trauma occurred to the eye with a dysplastic lesion in two patients. Dysplastic lesions were most frequently solitary and located temporal to the macula. Subretinal neovascularization accompanied two of the dysplastic lesions. The lesions were multifocal and present bilaterally in two patients. CONCLUSIONS: In fundus flavimaculatus, progressive lipofuscin storage is responsible for engorgement and hypertrophy of the RPE. Dysplastic lesions of the RPE probably result from reactive hyperplasia and fibrous metaplasia of RPE cells in response to acute disruption of fragile, hypertrophied RPE cells that may be enormously enlarged in the area of yellow flecks. This disruption may occur in response to trauma, focal inflammation, or other localized stimuli. Patients with fundus flavimaculatus should be cautioned concerning the possible role of trauma in causing dysplastic changes in the RPE and visual loss.

Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is a complex genetic disorder and the leading cause of severe vision loss in the elderly. The Stargardt disease gene (ABCR) has been proposed as a major genetic risk factor in AMD. The purpose of this study was to evaluate the authors' AMD population for the specific ABCR variants proposed previously as genetic risk factors for AMD. METHODS: The authors screened their AMD population (159 familial cases from 112 multiplex families and 53 sporadic cases) and 56 racially matched individuals with no known history of AMD from the same clinic population for evidence of the ABCR variants. Grading of disease severity was performed according to a standard protocol. Patients with extensive intermediate drusen or large soft drusen, drusenoid retinal pigment epithelial (RPE) detachments, geographic atrophy of the RPE, or evidence of exudative maculopathy were considered affected. Analysis for variants was performed by polymerase chain reaction amplification of individual exons of the ABCR gene with flanking primers and a combination of single-strand conformation polymorphism, heteroduplex analysis, and high-performance liquid chromatography. All abnormal conformers detected using these techniques were characterized by direct sequencing. RESULTS: The authors identified only two of the previously reported variants in their study population. Both variants occurred in sporadic cases, and none was found in familial cases or the randomly selected population. In addition, the authors identified several newly described polymorphisms and variants in both the AMD and control populations. CONCLUSIONS: Based on these initial findings, the authors suggest that ABCR is not a major genetic risk factor for AMD in their study population. Additional genetic studies are needed to more fully evaluate the role of ABCR in AMD.

Müller cell cone, an overlooked part of the anatomy of the fovea centralis: hypotheses concerning its role in the pathogenesis of macular hole and foveomacualr retinoschisis.

Poorly recognized by anatomists and pathologists is the cone-shaped zone of Müller cells that composes the central and inner part of the fovea centralis. The importance of these cells in the structural integrity of the macula, as a repository for xanthophyll, and in the pathogenesis of macular diseases, particularly regarding idiopathic macular hole and foveomacular schisis, is hypothesized.

A long-term follow-up of choroidal osteoma.

OBJECTIVE: To provide long-term follow-up information on a large series of patients with choroidal osteoma. METHODS: Review of patients with a diagnosis of choroidal osteoma who had been examined at the Bascom Palmer Eye Institute, Miami, Fla, or known to one of us (J.D.M.G.). Information was obtained from hospital medical records or by a questionnaire sent to referring ophthalmologists. Life-table analysis was used to study the loss of vision and development of choroidal neovascularization. RESULTS: We followed up 36 patients, 31 (89%) were female, mean age, 21 years (range, 5-54 years) for a mean of 10 years (range, 2-22 years). Growth was observed for 9 (41%) of 22 well-documented osteomas. The probability of loss of visual acuity to 20/200 or worse was 58% by 10 years and 62% by 20 years. The probability of developing choroidal neovascularization was 47% by 10 years and 56% by 20 years. Successful treatment of the choroidal neovascularization with laser photocoagulation was performed for 5 (25%) of 20 patients. CONCLUSIONS: Most patients with choroidal osteomas maintain good vision in at least 1 eye, but they have a high risk of developing choroidal neovascularization. When this occurs, only a minority can be successfully treated with laser photocoagulation.

Clinicopathologic correlations of surgically excised type 1 and type 2 submacular choroidal neovascular membranes.

PURPOSE: To correlate the histologic and clinical classification of type 1 (subretinal pigment epithelium) and type 2 (subsensory retina) choroidal neovascularization. METHODS: Ten eyes of 10 patients with surgically excised choroidal neovascularization that were routinely processed and could be histologically classified as having a type 1 or type 2 configuration were studied. The patients were clinically classified as having type 1 or type 2 choroidal neovascularization according to preoperative fundus appearance of both eyes and patient age. The histologic and clinical classifications were made in a masked fashion, and the results were compared. RESULTS: The histologic classification was type 1 and type 2 for three and seven specimens, respectively. The clinical classification matched the histologic classification in nine of 10 cases. Clinical fundus characteristics that distinguished type 2 choroidal neovascularization included a subretinal pigmented halo or pigmented plaque in the area of the choroidal neovascularization and sharply defined borders. Patients with type 1 membranes were on average older (76 years) than patients with type 2 membranes (53 years). CONCLUSIONS: It is generally possible to clinically ascertain by clinical fundus appearance and age of a patient whether subfoveal choroidal neovascularization represents a type 1 or type 2 configuration.