Fellow Eye Involvement Research Articles

Factors Affecting Rates of Visual Field Progression in Glaucoma Patients with Optic Disc Hemorrhage

Optic disc hemorrhage (DH) is an important risk factor for glaucoma progression. We sought to investigate factors affecting the rate of visual field (VF) progression after DH in glaucomatous eyes. Retrospective cohort study. Consecutive glaucoma patients from our Glaucoma Progression Study with > or =5 Swedish interactive threshold algorithm standard 24-2 VFs from 1999 through 2008. Disc photographs of all patients were evaluated for the presence of DH. Exclusion criteria were conditions other than glaucoma likely to affect the VF and insufficient number of VFs to create a slope after DH detection. Automated pointwise linear regression was used to determine the rate of VF loss after DH detection. Fast progression was defined as a global VF loss of > or =1.5 dB/year. Factors associated with a fast rate of VF loss after the detection of the DH were evaluated. Assessed variables included baseline (age, gender, intraocular pressure [IOP], central corneal thickness, VF mean deviation [MD], presence of migraine, Raynaud's phenomenon, low blood pressure, and exfoliation syndrome) and intercurrent data (DH recurrence, fellow eye involvement, glaucoma surgery, and IOP reduction). Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for each variable. Seventy-six eyes (76 patients; mean age, 68.3+/-10.9 years) were enrolled. Mean IOP and VF MD at the time of the DH detection were 16.6+/-3.8 mmHg and -5.6+/-5.7 dB, respectively. The mean global progression rate after DH was -1.1+/-1.3 dB/year (mean follow-up, 3.8+/-2.8 years). A rate of progression of > or =1.5 dB/year was found in 20 (26%) eyes. Multivariate logistic regression analysis revealed larger baseline MD (OR, 1.11; 95% CI, 1.01-1.20; P = 0.03) and older age (OR, 1.06; 95% CI, 1.01-1.13; P = 0.04) to be significant risk factors for fast progression after DH. Eyes with a baseline MD worse than -4.0 dB had a 270% increased risk of fast progression compared with those with an MD better than -4.0 dB. The presence of a DH in older subjects with a worse VF predicted further VF global MD deterioration by more than 5 dB within 4 years. These eyes should undergo careful and frequent disease surveillance and consideration should be given to more aggressive treatment.

Anterior Ischemic Optic Neuropathy After Intravitreal Injection of Bevacizumab

Bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent widely used for intravitreal treatment of neovascular and exudative ocular diseases, is generally free of complications, but lens injury, endophthalmitis, retinal detachment, subconjunctival hemorrhage, cataract progression, acute vision loss, central retinal artery occlusion, new or progressive subretinal hemorrhages, and tears of the retinal pigment epithelium have been reported (1). We describe a case of nonarteritic ischemic optic neuropathy (NAION) after intravitreal injection of bevacizumab, a complication not heretofore reported. A 72-year-old woman presented with vision loss in her right eye from exudative age-related macular degeneration (ARMD). She had had an episode of NAION 10 years earlier in the right eye. Best-corrected visual acuity was light perception in the right eye and finger counting at 1 m in the left eye. An afferent pupillary defect was present in the right eye. Intraocular pressures were 12 mmHg in both eyes. Slit-lamp examination was unremarkable except for a nuclear cataract in both eyes. Fundus examination and retinal fluorescein angiography revealed optic disc pallor and dry ARMD in right eye and an active subfoveal choroidal neovascularization in left eye (Fig. 1).FIG. 1: Fluorescein angiography performed 14 days before intravitreal bevacizumab injection shows optic disc hypoperfusion andmacular pigmentary changes in the right eye and a classic subfoveal choroidal neovascular membrane in the left eye (arrow).The left eye underwent an intravitreal injection of 2.5 mg/0.1 mL bevacizumab. Four weeks later, visual acuity was light perception in the right eye and finger counting at 2 m in the left eye with decreased activity of the neovascular complex. Two weeks later, she underwent an additional intravitreal injection of 2.5 mg/0.1 mL bevacizumab. One week after the injection, she reported visual loss in the left eye on awakening. On our examination, visual acuity was light perception in both eyes. Intraocular pressure was normal. Pupils were sluggishly reactive without afferent defect. The left optic nerve was now edematous with peripapillary hemorrhages (Fig. 2). She reported no symptoms of giant cell arteritis. Results of laboratory tests, including complete blood count, erythrocyte sedimentation rate, and serum C-reactive protein, were within the normal range.FIG. 2: Fundus photography and fluorescein angiography of the left eye performed 8 days after intravitreal bevacizumab injection show disc swelling with adjacent splinter hemorrhages and blockage of the peripapillary background fluorescence.Risk factors of NAION include crowding of the optic disc, systemic hypertension, diabetes, smoking, hyperlipidemia, and surgery (2). We propose the following possible mechanisms for NAION in our patient: Impaired autoregulatory and microcirculatory mechanisms of optic nerve circulation due to pan-VEGF blockade. The exact mechanism responsible for blood flow autoregulation in the optic nerve remains enigmatic (3). Recent studies have shown that vascular endothelial vasoactive agents play an important role in modulating the local vascular tone and perhaps in blood flow autoregulation (3). Impaired autoregulation of the optic disc circulation by atherosclerosis, with a possible contribution from serotonin and endothelin-mediated vasospasm, may play a role in the pathogenesis of idiopathic NAION (4). Inhibition of VEGF may influence this autoregulation in the microcirculation. In addition, a sudden drop in effective VEGF concentration may be responsible for closure of normal capillaries (5). Transient intraocular pressure (IOP) elevation after intravitreal injection of bevacizumab. A transient increase in IOP can lead to ischemia of the optic nerve head because of a decrease in perfusion pressure (6). Elevations in IOP immediately after intravitreal injections are common (7). However, this mechanism seems less likely because NAION occurred 7 days after the injection. The NAION is an incidental occurrence. The risk of fellow eye involvement in NAION is 15-24% within 5 years (8). Because our patient had an attack of NAION in right eye, she was susceptible to this event in the fellow eye. Given the widespread use of intravitreal anti-VEGF agents, a possible effect of VEGF blockade on optic nerve circulation merits further exploration. Hamid Hosseini, MD Mohammad Reza Razeghinejad, MD Poostchi Ophthalmic Research Center Shiraz University of Medical Sciences Shiraz, Iran [email protected]

Delayed fellow eye involvement in patients with Vogt–Koyanagi–Harada disease

Vogt–Koyanagi–Harada (VKH) disease is a multisystem autoimmune disorder directed against melanocyte-associated antigens in the skin, inner ear, meninges and uveal tract. Ocular VKH disease typically presents as an acute, bilateral,...

The Ischemic Optic Neuropathy Decompression Trial

N ONARTERITIC ANTERIOR ISCHEMIC OPTIC neuropathy (NAION) is the most common cause of acute optic nerve disease in the elderly and often results in severe visual loss. The average annual incidence has been estimated at 2.3 to 10.2 per 100 000 persons aged 50 years and older with about 1500 to 6000 new cases seen each year in the United States. Although the visual acuity in patients with NAION remains better than 20/60 in approximately 50% of affected patients, the visual field is invariably abnormal, and more than one-third of patients have vision worse than 20/200 in the affected eye. Second eye involvement occurs in approximately 15% to 20% of patients with NAION within 5 years and often results in a dramatic reduction in patient independence and quality of life. No therapy for acute NAION or prevention of fellow eye involvement has yet proved to be effective. In 1989, it was first suggested that optic nerve decompression surgery (ONDS) might improve vision, particularly in patients with a progressive form of NAION. The surgery involves making 2 or more slits or a window in the optic nerve sheath, allowing cerebrospinal fluid to escape, purportedly reducing the pressure surrounding the optic nerve. Subsequent publications reported a beneficial effect of ONDS, even in the nonprogressive form of NAION, while others were in disagreement about the efficacy. None of these reports were based on a randomized controlled trial, sample sizes were small, uniform visual testing procedures were not used, and progressive disease was not well defined. As surgery was being performed more frequently, it became imperative to test the procedure in a randomized clinical trial before use of the procedure became even more widespread. The Ischemic Optic Neuropathy Decompression Trial (IONDT) was a randomized, single-masked, controlled trial conducted at 25 US clinical centers, sponsored by the National Eye Institute. The objective of the IONDT was to assess the safety and efficacy of ONDS compared with observation alone in patients with NAION. Secondary objectives were to describe the demographic and clinical characteristics and the natural history of a large prospectively followed-up cohort of patients with NAION seen within 2 weeks of onset. Eligibility criteria for randomization to either ONDS or observation included a diagnosis of acute unilateral NAION in a patient aged 50 years or older and a visual acuity of 20/64 or worse and better than no light perception. Patients who were eligible except for having a visual acuity better than 20/64 were followed weekly and subsequently randomized only if their visual acuity fell to 20/64 or worse within 30 days (“late-entry group”). Standardized histories and examinations were obtained at 3, 6, 12, 18, and 24 months and annually thereafter by certified study personnel, and masked personnel performed outcome measures. Surgery was performed by experienced, certified study surgeons according to an explicit study protocol. A surgical quality-assurance committee developed and implemented a quality-assurance program, which included administration of surgical technique questionnaires, masked review of operative notes, and approval of a masked videotape of an ONDS performed by each study surgeon. Recruitment for the IONDT began in October 1992. On the recommendation of its data and safety monitoring committee, recruitment was stopped in October 1994. The preliminary results bearing on the primary outcome measure were reported in 1995 in the Journal of the American Medical Association and were based on data from 244 patients with NAION and visual acuity of 20/64 or worse, representing 125 patients randomized to observation and 119 to surgery. As regards visual improvement at 6 months (defined as an improvement of 3 lines or more), patients assigned to surgery did no better than patients who were observed without intervention; 32.6% of the surgery group improved compared with 42.7% of the observed group. Furthermore, patients who underwent surgery had a significantly greater risk of losing 3 or more lines of vision at 6 months; 23.9% in the surgery group worsened compared with 12.4% in the cohort who did not have surgery. No difference in treatment effect was observed between patients with progressive NAION and all others. The conclusion of this first publication from the IONDT was that ONDS for NAION is not effective, may be harmful, and should be abandoned. This caveat was reinforced by a January 3, 1995, flier from the National Eye Institute. The articles that follow are part of an ongoing series that aims to review collaborative prospective studies supported by the National Eye Institute. The first article, written by investigators, will remind readers of the rationale, goals, methods, findings, and recommendations. The second article, written by an expert who did not participate in the investigations, will offer a constructive critique and attempt to estimate the impact of the study on the practice of ophthalmology.

Anterior Ischemic Optic Neuropathy in Patients Younger than 50 Years

To characterize anterior ischemic optic neuropathy (AION) in patients younger than 50 years. Retrospective study. Records of all AION patients seen between 1989 and 2006 were reviewed. Patients younger than 50 years when initial visual loss occurred were included. Of 727 consecutive patients with AION, 169 (23%) were younger than 50 years (median, 43 years; range, 13 to 49 years; 58% men; 93% White). Involvement was unilateral in 59% of patients and bilateral in 41%. At least one cardiovascular risk factor was found in 74% of patients. Hypercoagulable states and vasculitis were found in 8%. An underlying small or anomalous optic disk was found in 92% of eyes (210/230). Isolated disk anomalies (without systemic risk factors) were present in 26% of eyes. Final visual acuities were 20/40 or better in 64% of eyes and 20/200 or worse in 22%. Among patients with bilateral involvement, final visual acuity was similar in the two eyes in 70% of patients. Anemia and type I diabetes were associated significantly with fellow eye involvement. Recurrent AION in the same eye occurred in 6% of patients. AION in younger patients is not uncommon and represents 23% of AION patients in a tertiary neuro-ophthalmic service. Except for giant cell arteritis, ocular and systemic risk factors and associated disorders are similar to those described in older AION patients. Younger AION patients have better visual acuity outcomes but a higher risk of fellow eye involvement than older AION patients.

The Natural History and Prognosis of Neovascular Age-Related Macular Degeneration: A Systematic Review of the Literature and Meta-analysis

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) (approximately 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.

Acute Retinal Necrosis

Acute retinal necrosis (ARN) is an uncommon intraocular inflammatory syndrome characterized by severe and diffuse uveitis, retinal vasculitis, and retinal necrosis. It is typically described to occur in immunocompetent patients, but can also be found in immunocompromised subjects. Varicella-zoster virus (VZV), herpes simplex virus (HSV 1 and 2), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) have been implicated in the etiology of ARN. The characteristic features of the disease include iridocyclitis, vitritis, retinal vasculitis, and retinal necrosis. Bilateral involvement occurs in two-thirds of the patients, frequently in the first six weeks, but sometimes months to years later. Retinal detachment occurs in 75% of the cases. The diagnosis of ARN is usually based in clinical features. The use of polymerase chain reaction (PCR) in aqueous humor samples is useful to identify the etiology of the disease. The treatment of ARN includes intravenous acyclovir, corticosteroids and aspirin. To prevent fellow eye involvement, intravenous acyclovir is followed by oral acyclovir for 14 weeks. Alternatives to acyclovir include ganciclovir, foscarnet, famcyclovir, brivudine, and valgancyclovir.

Familial exudative vitreoretinopathy mimicking persistent hyperplastic primary vitreous

Purpose: To report an unusual case of familial exudative vitreoretinopathy in an infant. Methods: Case report. A 6-day-old girl had unilateral microphthalmia in the right eye, with a retrolental plaque initially diagnosed as persistent hyperplastic primary vitreous. Three months later, peripheral retinal vascular changes and a fibrovascular ridge were noted in the left eye, suggesting familial exudative vitreoretinopathy as the cause in both eyes. Results: The microphthalmic right eye was unsalvageable. The left eye developed an exudative retinal detachment despite photocoagulation of the peripheral avascular retina. Additional cryotherapy resulted in resolution of the detachment and regression of the vascular changes. Conclusions: With highly asymmetric involvement, neonatal familial exudative vitreoretinopathy can mimic persistent hyperplastic primary vitreous. Fellow eye involvement can progress rapidly.

Incidence of idiopathic full-thickness macular holes in fellow eyes: A 5-year prospective natural history study

This study aimed to determine the incidence of idiopathic full-thickness macular hole (FTMH) in normal fellow eyes and to evaluate the role of electrodiagnostic and psychophysical tests in identifying eyes at risk. A prospective longitudinal natural history study of a cohort of patients with unilateral holes and normal, asymptomatic fellow eyes without posterior vitreous detachment was conducted. Subjects underwent baseline examination, pattern reversal electroretinography, electro-oculography (EOG), and color contrast sensitivity (CCS) testing for protan, deutan, and tritan thresholds and were recalled for clinical examination at 18 months and 5 years. At baseline, 114 patients were examined. Eighty were available for review at 18 months, of whom 6 had full-thickness macular holes develop in the fellow eye. At 5 years, 67 of the remaining 74 patients who had not developed holes at 18 months were re-examined and a further 5 were found to have holes develop in the fellow eye. A posterior vitreous detachment without hole formation had developed in 20 fellow eyes at 5 years. Although mean pattern reversal electroretinography and EOG responses were within normal limits in affected and fellow eyes at baseline, mean CCS protan, deutan, and tritan thresholds were elevated significantly in affected eyes at baseline (P = 0.0001). Unaffected fellow eyes showed normal mean protan and deutan thresholds, but significantly elevated mean tritan thresholds (P = 0.01) at baseline. Mean tritan CCS loss was, however, similar in fellow eyes in which holes later developed and in fellow eyes in which holes did not. The Kaplan-Meier estimated risk of fellow eye involvement is 15.6% (range, 8.4%-22.3%; P = 0.05) at 5 years. Although electrodiagnostic and psychophysical testing was not predictive of fellow eye involvement, tritan CCS loss at baseline, in apparently normal fellow eyes, may indicate subclinical foveal dysfunction, the nature of which is unclear.

Twenty Years' Delay of Fellow Eye Involvement in Herpes Simplex Virus Type 2-Associated Bilateral Acute Retinal Necrosis Syndrome

To describe a case of acute retinal necrosis with concurrent encephalitis and determine the causative virus. The patient had a history of presumed acute retinal necrosis in the left eye at the age of 8 years and recurrent genital herpes. Diagnostic anterior chamber puncture of the eye and lumbar puncture for laboratory analysis. Polymerase chain reaction identified herpes simplex virus type 2 in the eye, and local antibody production to herpes simplex virus was demonstrated in the aqueous of this eye and in the cerebrospinal fluid. Herpes simplex virus type 2 may cause bilateral acute retinal necrosis with long delay of fellow eye involvement and concurrent encephalitis.

Delayed Fellow Eye Involvement in Acute Retinal Necrosis Syndrome

We studied a case of acute retinal necrosis in which a 30-year delay occurred between involvement of the first and fellow eyes. After systemic treatment with acyclovir and prednisolone, the fellow eye developed a retinal detachment requiring vitrectomy and silicone oil tamponade. The fellow eye retained a useful Snellen acuity of 20/120. In a patient who has had acute retinal necrosis, any symptoms or signs in the fellow eye, even several decades later, should alert the examining physician to the possibility of delayed involvement of the fellow eye.

Visual Morbidity in Giant Cell Arteritis: Clinical Characteristics and Prognosis for Vision

To characterize visual morbidity in giant cell arteritis and to assess prognosis with respect to treatment. Record review of 185 patients with coded diagnosis of giant cell (cranial) arteritis examined at the Bascom Palmer Eye Institute from January 1, 1980, to January 31, 1993. Forty-five patients with biopsy-proven giant cell arteritis had visual symptoms, and 41 individuals (63 eyes) lost vision. The visual loss was unilateral in 19 patients (46%), sequential in 15 (37%), and simultaneous in 7 (17%). Anterior ischemic optic neuropathy developed in 88% of eyes, visual acuity was 20/200 or worse in 70%, 21% had no light perception, and the majority of field defects in testable eyes, aside from central scotomas associated with loss, showed altitudinal or arcuate patterns. Six patients lost vision during corticosteroid therapy for systemic symptoms of giant cell arteritis, whereas in 39 patients visual symptoms prompted steroid treatment. For visual symptoms, 25 patients received intravenous methylprednisolone, whereas 20 received oral prednisone alone. In the 41 patients with visual loss, vision was unchanged in 20 (49%), it worsened in 7 (17%), and it improved in 14 (34%). Subsequent fellow eye involvement was observed only with oral therapy, and a greater percentage of patients (9/23 [39%] versus 5/18 [28%]) improved after intravenous treatment. In the authors' series, patients with visual loss due to giant cell arteritis had a 34% chance for some improvement in visual function after corticosteroid treatment. Intravenous therapy may diminish the likelihood of fellow eye involvement and was associated with a slightly better prognosis for visual improvement.