Year 2 efficacy results of 2 randomized controlled clinical trials of pegaptanib for neovascular age-related macular degeneration.

OBJECTIVE: To evaluate the efficacy of a second year of pegaptanib sodium therapy in patients with neovascular age-related macular degeneration (AMD). DESIGN: Two concurrent, multicenter, randomized, double-masked, sham-controlled studies (V.I.S.I.O.N. [Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization] trials). PARTICIPANTS: Patients with all angiographic neovascular lesion compositions of AMD were enrolled. In combined analyses, 88% (1053/1190) were re-randomized at week 54, and 89% (941/1053) were assessed at week 102. INTERVENTIONS: At week 54, those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks (8 injections). Those initially assigned to sham were re-randomized to continue sham, discontinue sham, or receive 1 of 3 pegaptanib doses. MAIN OUTCOME MEASURES: Mean change in visual acuity (VA) over time and mean change in the standardized area under the curve of VA and proportions of patients experiencing a loss of > or =15 letters from week 54 to week 102; losing <15 letters (responders) from baseline to week 102; gaining > or =0, > or =1, > or =2, and > or =3 lines of VA; and progressing to legal blindness (20/200 or worse). RESULTS: In combined analysis, mean VA was maintained in patients continuing with 0.3-mg pegaptanib compared with those discontinuing therapy or receiving usual care. In patients who continued pegaptanib, the proportion who lost >15 letters from baseline in the period from week 54 to week 102 was half (7%) that of patients who discontinued pegaptanib or remained on usual care (14% for each). Kaplan-Meier analysis showed that patients continuing 0.3-mg pegaptanib for a second year were less likely to lose > or =15 letters than those re-randomized to discontinue after 1 year (P<0.05). The proportion of patients gaining vision was higher for those assigned to 2 years of 0.3-mg pegaptanib than receiving usual care. Progression to legal blindness was reduced for patients continuing 0.3-mg pegaptanib for 2 years. CONCLUSIONS: Continuing visual benefit was observed in patients who were randomized to receive therapy with pegaptanib in year 2 of the V.I.S.I.O.N. trials when compared with 2 years' usual care or cessation of therapy at year 1.

Pegaptanib sodium for neovascular age-related macular degeneration: two-year safety results of the two prospective, multicenter, controlled clinical trials.

OBJECTIVE: To evaluate the safety of pegaptanib sodium injection, a specific vascular endothelial growth factor (VEGF) antagonist, in the treatment of neovascular age-related macular degeneration (AMD) during 2 years of therapy. DESIGN: Two concurrent, prospective, randomized, multicenter, double-masked, sham-controlled studies. METHODS: Patients with all angiographic choroidal neovascularization lesion compositions of AMD received either intravitreous pegaptanib sodium (0.3 mg, 1 mg, 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were re-randomized (1:1) to continue or discontinue therapy for 48 more weeks; sham-treated patients were re-randomized (1:1:1:1:1) to continue sham, discontinue, or receive one of the pegaptanib doses. MAIN OUTCOME MEASURES: All reported adverse events, serious adverse events, and deaths. PARTICIPANTS: In year 1, 1190 subjects received at least one study treatment (0.3 mg, n = 295; 1 mg, n = 301; 3 mg, n = 296; sham, n = 298); 7545 intravitreous injections of pegaptanib were administered. In year 2, 425 subjects (0.3 mg, n = 128; 1 mg, n = 126; 3 mg, n = 120; sham, n = 51) continued the same masked treatment as in year 1 and received at least one study treatment in year 2; 2663 intravitreous injections of pegaptanib were administered in these subjects. RESULTS: All doses of pegaptanib were well tolerated. The most common ocular adverse events were transient, mild to moderate in intensity, and attributed to the injection preparation and procedure. There was no evidence of an increase in deaths, in events associated with systemic VEGF inhibition (e.g., hypertension, thromboembolic events, serious hemorrhagic events), or in severe ocular inflammation, cataract progression, or glaucoma in pegaptanib-treated patients relative to sham-treated patients. In year 1, serious injection-related complications included endophthalmitis (12 events, 0.16%/injection), retinal detachment (RD) (6 events [4 rhegmatogenous, 2 exudative], 0.08%/injection), and traumatic cataract (5 events, 0.07%/injection). Most cases of endophthalmitis followed violations of the injection preparation protocol. In patients receiving pegaptanib for >1 year, there were no reports of endophthalmitis or traumatic cataract in year 2; RD was reported in 4 patients (all rhegmatogenous, 0.15%/injection). CONCLUSION: The 2-year safety profile of pegaptanib sodium is favorable in patients with exudative AMD.

Regression of cytomegalovirus retinitis with zidovudine. A clinicopathologic correlation.

A 55-year-old man with the acquired immunodeficiency syndrome had cytomegalovirus (CMV) retinitis develop in his left eye. The patient declined treatment with ganciclovir but elected to be treated with zidovudine. Two months later his CMV retinitis regressed, and it remained inactive for a total of 9 months. The most likely explanation was zidovudine-mediated improvement in the patient's immune function with subsequent suppression of the CMV retinitis in the left eye. The patient ultimately and preterminally had CMV retinitis develop in his right eye. He subsequently died and his eyes were examined at autopsy. Active CMV retinitis lesions were noted in the right eye while inactive scars were noted in the left eye. Immunoperoxidase staining and in situ hybridization studies demonstrated the presence of CMV in the right eye but not in the left eye. While ganciclovir remains the treatment of choice for CMV retinitis, zidovudine treatment may have a beneficial effect on CMV retinitis in some patients.

The risk of cerebrovascular and cardiovascular disease in patients with anterior ischemic optic neuropathy.

Of 217 patients in whom anterior ischemic optic neuropathy (AION) was diagnosed during the period from 1975 to 1985, verifiable medical information was obtained for 212 (98%). Over a median follow-up period of three years, no group of patients had an increased mortality rate over that of age-, sex-, and race-matched controls; however, patients with "idiopathic" AION and patients with systemic hypertension who developed nonarteritic AION had a statistically significant increased risk of experiencing cerebrovascular events and myocardial infarctions compared with appropriately matched control groups. In view of the findings of our study, we suggest that patients with idiopathic AION and hypertensive patients who develop nonarteritic AION undergo a complete physical examination, cardiac evaluation, tests of carotid artery patency, and careful medical follow-up to attempt to prevent subsequent cerebrovascular or cardiovascular events.

Observations on patients with idiopathic macular holes and cysts.

We reexamined 96 patients with macular holes or cysts. The mean follow-up period was 4.7 years. Of 19 eyes with macular cysts, only two (10.5%) showed progression to a macular hole. In 15 (79%) of those 19 eyes, the cyst disappeared. Of 80 patients with a macular hole or cyst in one eye and a normal fellow eye, a hole developed in the fellow eye in only one patient (1.2%) and a cyst developed in the fellow eye in only two patients (2.5%). Of 66 eyes with a stage 3 full-thickness macular hole, three eyes (5%) showed resolution without any sign of a hole. Our results suggest a favorable prognosis for normal fellow eyes of patients with macular holes or cysts and for eyes with cysts. Eyes with full-thickness macular holes have a less favorable prognosis, although their natural history may not be as poor as previously thought.

Digital indocyanine green videoangiography of central serous chorioretinopathy.

BACKGROUND: The pathogenesis of central serous chorioretinopathy (CSC) is poorly understood. Abnormalities in the choroidal circulation have been hypothesized to be causative factors. Fluorescein angiography has not been particularly useful in identifying specific choroidal defects in CSC, largely because of inherent limitations in imaging with this technique. Recent technologic advances in digital indocyanine green videoangiography allow enhanced imaging of the choroid and other subretinal structures in comparison with fluorescein angiography. METHODS: We performed digital indocyanine green videoangiography in 29 consecutive eyes with CSC and compared our results with clinical and fluorescein angiographic findings. RESULTS: Several newly recognized subretinal abnormalities in CSC were noted with digital indocyanine green videoangiography, including (1) presumed hyperpermeability of the choroidal circulation surrounding active retinal pigment epithelial leaks, (2) additional focal and multifocal areas of presumed choroidal hyperpermeability not associated with abnormalities detectable by fluorescein angiography or clinical examination, and (3) multiple presumed "occult" serous retinal pigment epithelial detachments with a characteristic indocyanine green videoangiographic pattern. CONCLUSION: We suggest that the pathogenesis of CSC may be due to a choroidal vascular hyperpermeability with and without associated active pigment epithelial leaks and multiple presumed "occult" serous retinal pigment epithelial detachments. Based on these findings, a hypothetical model can be constructed related to the pathogenesis of CSC, beginning with choroidal abnormalities that secondarily affect the retinal pigment epithelium and neurosensory retina.

Indocyanine green-guided laser photocoagulation of focal spots at the edge of plaques of choroidal neovascularization.

OBJECTIVE: To determine whether indocyanine green-guided laser photocoagulation of focal spots at the edge of plaques of neovascularization is beneficial for patients with untreatable occult choroidal neovascularization by fluorescein imaging. PATIENTS: A pilot series of 23 eyes were identified that had untreatable occult choroidal neovascularization secondary to age-related macular degeneration with focal spots at the edge of a plaque of neovascularization on the indocyanine green study. After informed consent was obtained, indocyanine green-guided laser photocoagulation was applied solely to the focal spot at the edge of the plaque. RESULTS: Anatomical success with resolution of the exudative findings was noted in 15 (79%) of 19 eyes at 6 months, 13 (68%) of 19 eyes at 12 months, and six (37.5%) of 16 eyes at 24 months. The median follow-up period was 18 months (range, 3 to 44 months). Visual acuity was stabilized or improved in nine (69%) of 13 successfully treated eyes at 1 year. Of the successfully treated cases at 1 year, nine (69%) of 13 had a final visual acuity of 20/100 or better. CONCLUSIONS: Our preliminary study of indocyanine green-guided laser photocoagulation of focal spots at the edge of plaques of neovascularization suggests that this technique may improve the visual prognosis of these patients with presently untreatable disease. A prospective, randomized, controlled clinical trial is warranted to evaluate this treatment approach.

The expanding clinical spectrum of unilateral acute idiopathic maculopathy.

OBJECTIVE: To report on new features of unilateral acute idiopathic maculopathy (UAIM). PATIENTS: We have evaluated an additional 17 patients with UAIM since 1991. This is a report of new features of the maculopathy noted in seven patients from this new series. RESULTS: New clinical findings in UAIM included eccentric macular lesions, subretinal exudation, papillitis, and bilaterality. The occurrence of UAIM in association with pregnancy and human immunodeficiency virus was also observed. CONCLUSIONS: The description of these newly reported features broadens our understanding of the nature of UAIM. With recognition of the expanded clinical spectrum of this disorder, a more confident approach to diagnosis and management may be achieved.

Subfoveal choroidal neovascular membranes in age-related macular degeneration. Visual prognosis in eyes with relatively good initial visual acuity.

We determined the visual prognosis of 94 eyes in 92 patients having age-related macular degeneration, a discrete choroidal neovascular membrane directly under the center of the foveal avascular zone (subfoveal), and an initial visual acuity of 20/100 or better. Of the patients who were reexamined 24 months following their initial presentation, 77% had lost at least four lines of vision and 64% had lost at least six lines. Estimation of visual loss using a conservative assessment procedure showed four-line visual loss in 65% of the patients and six-line loss in 50%. In general, the better the visual acuity at the initial examination, the more likely the patient was to have a smaller choroidal neovascular membrane. These results suggest that it may be reasonable to consider a randomized clinical trial of laser photocoagulation for this group of patients with a relatively poor visual prognosis.

Ophthalmic manifestations of leukemia.

We prospectively examined the eyes of 120 patients with leukemia. Only 38% of patients had normal results of examination. Leukemic infiltrates were present in 3% of patients, other findings related to leukemia were seen in 39% of patients, and 20% of patients had unrelated abnormalities. Visual loss was seen in at least 5% of the patients in this study.

Interferon-associated retinopathy.

Interferon alfa is used to treat various systemic disorders and recently has been suggested as a possible treatment for choroidal neovascularization. We report 10 cases of retinal ischemia associated with the use of interferon alfa for various illnesses. The retinal findings include cotton-wool spot formation, capillary nonperfusion, arteriolar occlusion, and hemorrhage. The retinal complications may sometimes be reversible when treatment is stopped. Our findings emphasize the need to have patients who are receiving interferon alfa therapy monitored for these retinal complications, which may rarely be associated with permanent loss of vision secondary to closure of retinal capillaries.

A pilot study of indocyanine green videoangiography-guided laser photocoagulation of occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: To evaluate the use of digital indocyanine green videoangiography in patients with clinical and fluorescein angiographic evidence of "occult" choroidal neovascularization in age-related macular degeneration and to investigate indocyanine green videoangiography-guided laser photocoagulation as a therapeutic approach. METHODS: Three hundred forty-seven consecutive patients with exudative age-related macular degeneration and symptoms and clinical manifestations of occult choroidal neovascularization were studied with indocyanine green videoangiography. Patients were selected for laser treatment, using conventional guidelines, when indocyanine green videoangiography demonstrated a well-delineated area of hyperfluorescence, presumed to be a focal area of choroidal neovascularization. RESULTS: Seventy-nine (23%) of 347 eyes were found to have a localized and definable lesion that was potentially amenable to laser photocoagulation therapy; 44 (56%) of these 79 treated eyes had complete resolution of their exudative manifestations. Visual acuity improvement was noted in 10 (13%) of 79 eyes, and stabilization of vision achieved in 42 eyes (53%). CONCLUSION: Laser photocoagulation treatment guided by indocyanine green videoangiography was shown to produce promising anatomical and visual improvement in a small number of patients with occult choroidal neovascularization secondary to age-related macular degeneration. This pilot study warrants further research to investigate the efficacy and safety of this form of treatment.

A pilot study of digital indocyanine green videoangiography for recurrent occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: Digital indocyanine green videoangiography (ICG-V) was used to study recurrent choroidal neovascularization (CNV) in patients with the clinical and fluorescein angiographic findings indicative of ill-defined, or recurrent occult, CNV (RO-CNV). The use of ICG-V-guided laser caphotocoagulation as an alternative form of treatment was also investigated when a well-delineated area of CNV was imaged with this technique. METHODS: A consecutive series of 66 patients were studied who presented with exudative age-related macular degeneration and symptoms and clinical manifestations of recurrent CNV in which fluorescein angiography did not reveal classic, or well-defined, neovascularization. Patients were selected for laser treatment based on conventional guidelines if ICG-V imaged a well-delineated area of recurrent CNV. RESULTS: Indocyanine green videoangiography showed late staining that was consistent with recurrent CNV in 64 (97%) of these 66 patients with RO-CNV. Twenty-nine (44%) of the 66 were eligible for laser treatment, and 18 (62%) of these 29 patients experienced successful anatomic and visual results, which were defined as resolution of the exudative manifestations and improvement or stabilization (+/- 1 line on a Snellen chart) of vision. CONCLUSIONS: This pilot study suggests that ICG-V is of value in imaging patients with RO-CNV after laser photocoagulation for CNV secondary to age-related macular degeneration. Laser treatment of RO-CNV with ICG-V guidance may be successful both anatomically and functionally in a promising number of these otherwise untreatable cases. Further studies are necessary to validate these preliminary findings.

Polypoidal choroidal vasculopathy and neovascularized age-related macular degeneration.

OBJECTIVE: To determine the nature and frequency of polypoidal choroidal vasculopathy (PCV) in a series of patients suspected of having neovascularized age-related macular degeneration (AMD). METHODS: A prospective analysis of 167 consecutive, newly diagnosed patients aged 55 years or older with presumed neovascularized AMD was performed. All patients were examined with fundus biomicroscopy as well as fluorescein and indocyanine green angiography. RESULTS: Choroidal neovascularization secondary to AMD was diagnosed in 154 (92.2%) of 167 patients; 13 (7.8%) patients had PCV. The patients affected by PCV were younger than those with AMD (P = .01). Peripapillary choroidal neovascularization was seen in 3 (1.9%) of 154 patients with AMD and 3 (23.1%) of 13 patients with PCV (P = .006). Significant drusen were present in 63 (70%) of 90 fellow eyes with unilateral AMD compared with only 1 (16.7%) of 6 eyes with PCV (P = .02). Only 5 patients with AMD (3.2%) were nonwhite compared with 3 patients with PCV (23.1%) (P = .02). CONCLUSIONS: A measurable number of elderly patients with findings suggestive of neovascularized AMD and serosanguineous macular manifestations will instead have PCV. Polypoidal choroidal vasculopathy can occur in any sex or race, but is more commonly seen in the peripapillary area, without associated drusen, and in nonwhite patients. It is important to differentiate AMD from PCV because there are significant differences in the demographic risk profile, natural course, visual prognosis, and management of these patients.

Macular hole.

A macular hole is a full-thickness defect of retinal tissue involving the anatomic fovea, thereby affecting central visual acuity. Macular holes have been associated with myriad ocular conditions and originally were described in the setting of trauma. The pathogenesis of idiopathic, age-related macular holes remains unclear despite a litany of theories. Recently, Gass has described an updated biomicroscopic classification of macular holes and postulated that tangential vitreous traction may play a role. Cellular components surrounding the rim of macular holes may also contribute tangential traction forces and elevate the rim. Pseudomacular holes may be mistaken for macular hole lesions, despite careful clinical examination. Careful biomicroscopic examination with a contact lens and use of the Watzke and laser aiming beam tests help to ensure accurate diagnosis. Newer imaging technology, such as optical coherence tomography, helps distinguish true macular holes from pseudoholes and may provide additional insight into the pathogenesis of this condition. Surgical management with or without pharmacosurgical adjuncts can improve vision in select cases. The most common surgical complication is progressive lens opacification in phakic patients.

Pseudohypopyon of orange pigment overlying a stable choroidal nevus.

PURPOSE: To report an unusual case of orange pigment pseudohypopyon overlying a choroidal nevus. METHODS: Observational case report. A 45-year-old man presented with best-corrected visual acuity of 20/25 and metamorphopsia in the right eye secondary to localized subfoveal fluid. The detachment displayed a peculiar appearance of layered orange pigment, like a pseudohypopyon in its inferior aspect. Closer inspection revealed an underlying choroidal nevus and no choroidal neovascular membrane. RESULTS: After 31 months of follow-up without treatment, the size of the nevus and visual acuity remained stable and metamorphopsia continued to resolve as the orange pigment and the subretinal fluid disappeared completely. CONCLUSION: An otherwise stable choroidal nevus can display overlying clumps of orange pigment and rarely massive accumulation of orange pigment in the form of a pseudohypopyon. Orange pigment pseudohypopyon can spontaneously resolve with preserved visual acuity.

Subretinal fibrosis after laser photocoagulation for diabetic macular edema.

Seven eyes had subretinal fibrosis after grid laser photocoagulation for diabetic macular edema. The fibrosis caused persistent loss in visual acuity, and in six of the seven eyes, was not associated with detectable laser-induced Bruch's membrane rupture or subretinal hemorrhage. Choroidal neovascularization was detected in only one patient, who was notably younger (27 years) than the median age of 70 years in this series. The median preoperative visual acuity was 20/80 (range, 20/40 to 20/400); the median postoperative visual acuity was 20/400 (range, 20/80 to counting fingers). The subretinal fibrosis was detected at a median of three months (range, 14 days to 4 1/2 months) after laser therapy. In one of five bilaterally treated patients (20%), subretinal fibrosis developed in both eyes. Subretinal fibrosis may be caused by undetected choroidal neovascularization or by excessive proliferation after stimulation of an aged retinal pigment epithelium. Subretinal fibrosis may be a potential cause of loss in visual acuity after laser treatment for diabetic macular edema.

Systemic findings associated with central serous chorioretinopathy.

PURPOSE: To determine systemic factors associated with central serous chorioretinopathy. METHODS: In a retrospective study, 230 consecutive patients with central serous chorioretinopathy examined in a referral setting were compared with a historical gender-matched and age-matched control group of 230 patients with ocular findings who were examined in the same referral setting. RESULTS: The median age of the patients was 49.8 years, and of the control subjects, 50.0 years. The male-female ratio for both groups was 2.7:1. Patients with central serous chorioretinopathy were more likely to use psychopharmacologic medications (odds ratio = 2.6; 95% confidence interval = 1.30 to 5.19; P = .0049) and corticosteroids (odds ratio = 3.17; 95% confidence interval = 1.30 to 7.70; P = .0067) and were more likely to have hypertension (odds ratio = 2.25; 95% confidence interval = 1.39 to 3.63; P = .0008) than were the control subjects. CONCLUSIONS: This study identified psychopharmacologic medication use, corticosteroid use, and hypertension as factors associated with central serous chorioretinopathy. These findings reinforce the concept that stress and adaptations to stress play a role in this disorder. The findings of possible associations between central serous chorioretinopathy and both hypertension and corticosteroid usage suggest that these modifiable factors may influence morbidity of central serous chorioretinopathy.

Visual function following optic canal decompression via craniotomy.

Visual function was assessed in 15 eyes of 11 patients who underwent unilateral (seven patients) or bilateral (four patients) optic canal decompression for presumed compressive optic neuropathies. Both immediate and long-term postoperative vision was evaluated in all eyes. Over 90% of the eyes that had undergone nerve decompression had either the same or improved visual acuity and visual field immediately following surgery. In this group of patients there were no deaths and there was only one postoperative complication, a transient dysphasia caused by an epidural hematoma that was evacuated. Long-term follow-up evaluations revealed that most of the eyes retained their immediate postoperative visual function or showed gradual visual improvement with time. The results of this series as well as a review of the available literature indicate that optic canal decompression via craniotomy can be a safe procedure and that it appears to have lasting visual benefit in many patients.

Indocyanine green videoangiography: current status.

Indocyanine-green (ICG) angiography has experienced a rejuvenated interest in the past few years because of improvements in technological systems. After three years of experience with evolving digital technology, we have reviewed our experience to provide an update on potential applications in a variety of choroidopathies. Based on 3,000 cases studied with ICG angiography, we evaluated the diagnostic value of the procedure in choroidal abnormalities including ischemic, tumor, idiopathic, inflammatory, and neovascularized diseases. ICG angiography is still of limited clinical value in ischemic diseases because of a relatively poor imaging potential for the choriocapillaris. The procedure has not yet provided information which is of significant value in the evaluation and management of choroidal tumors. Valuable information has been provided on the fundamental pathogenesis of certain idiopathic diseases. Preliminary experience in inflammatory diseases is very promising. A genuine advance in imaging of "occult"-choroidal neovascularization has been provided by the diagnostic technique. Improved delineation of these vessels offers opportunities for ICG-guided laser treatment.