Pegaptanib sodium for neovascular age-related macular degeneration: third-year safety results of the VEGF Inhibition Study in Ocular Neovascularisation (VISION) trial.

AIMS: To evaluate the safety of up to 3 years of pegaptanib sodium therapy in the treatment of neovascular age-related macular degeneration (NV-AMD). METHODS: Two concurrent, prospective, multicentre, double-masked studies randomised subjects with all angiographic lesion compositions of NV-AMD to receive intravitreous pegaptanib sodium (0.3, 1 and 3 mg) or sham injections every 6 weeks for 54 weeks. Those initially assigned to pegaptanib were rerandomised to continue or discontinue therapy for 48 more weeks; sham-treated subjects continued sham, discontinued or received pegaptanib. At 102 weeks, subjects receiving pegaptanib 0.3 mg or 1 mg in years 1 or 2 continued; those receiving pegaptanib 3 mg or who did not receive treatment in years 1 and 2 were rerandomised to 0.3 mg or 1 mg for year 3. RESULTS: As in years 1 and 2, pegaptanib was well tolerated in year 3. Adverse events were mainly ocular in nature, mild, transient and injection-related. Serious adverse events were rare. No evidence of systemic safety signals attributed to vascular endothelial growth factor inhibition arose in year 3. There were no findings in relation to vital signs or electrocardiogram results suggesting a relationship to pegaptanib treatment. CONCLUSION: The 3-year safety profile of pegaptanib sodium was favourable in patients with NV-AMD.

Natural history of choroidal neovascularization in high myopia.

High myopia, or pathologic myopia, usually refers to a condition in which individuals have greater than 6 diopters of myopia or an axial length greater than 26 to 27 mm. The natural history of choroidal neovascularization in high myopia is variable, and reports to date have some conflicting information, but analysis shows fairly poor final visual outcomes. This outcome complicates recommendations for treatment and must be considered in future studies aimed at managing this disease.

Visual acuity outcomes of patients 50 years of age and older with high myopia and untreated choroidal neovascularization.

OBJECTIVE: To evaluate visual outcomes of untreated submacular choroidal neovascularization (CNV) in patients 50 years of age and older with high myopia. DESIGN: Retrospective observational case series. PARTICIPANTS: Twenty-two eyes in 22 patients were studied. All were 50 years of age and older with myopia of 6.0 diopters (D) or greater or an axial length of 25.5 mm or greater. Patients had untreated CNV documented by clinical examination and fluorescein angiography at two medical centers between 1986 and 1997. INTERVENTION: Demographic and clinical data were abstracted from patients' medical records. MAIN OUTCOME MEASURE: Visual acuity at 1 year after CNV diagnosis. RESULTS: The study included 22 eyes of 22 patients (mean age, 63.1 years; mean refraction, -11.0 D). Baseline visual acuity (VA) in the study eye was 20/40 or greater in 2 (9%) patients, 20/50 to 20/150 in 9 (41%) patients, and 20/200 or less in 11 (50%) patients. Drusen were present in seven (32%) eyes, and lacquer cracks were noted in ten (45%) eyes. Mean refractive error was -7.0 D for patients with drusen and -12.5 D for patients without drusen. Choroidal neovascularization was less than 0.25 disc diameters (DD) in 11 (50%) eyes, 0.25 to 0.5 DD in 5 (23%) eyes, and greater than 0.5 DD in 6 (27%) eyes. Visual acuity in the study eye 1 year after CNV diagnosis was 20/40 or greater in 3 (14%) patients, 20/50 to 20/150 in 3 (14%) patients, and 20/200 or less in 16 (73%) eyes. The presence of drusen was significantly associated with older age and a lower degree of myopia but was not associated with size of the CNV or visual acuity outcome. CONCLUSION: When compared to patients younger than 50 years of age with high myopia and CNV reported in previous publications, the patients in the current series generally have poorer visual outcomes.

Long-term tamoxifen citrate use and potential ocular toxicity.

PURPOSE: To estimate the prevalence of abnormalities in visual function and ocular structures associated with the long-term use of tamoxifen citrate. METHODS: A single-masked, cross-sectional study involving multiple community and institutional ophthalmologic departments was conducted with a volunteer sample of 303 women with breast cancer currently taking part in a randomized clinical trial to determine the efficacy of tamoxifen (20 mg/day) in preventing recurrences. Participants included women who had never been on drug (n=85); women who had taken tamoxifen for an average of 4.8 years, then been off the drug for an average of 2.7 years (n=140); and women who had been on tamoxifen continuously for an average of 7.8 years (n=78). Women were evaluated by questionnaire, psychophysical testing, and clinical examination to determine any abnormalities in visual function and the comparative prevalences of corneal, lens, retinal, and optic nerve pathology. RESULTS: There were no cases of vision-threatening ocular toxicity among the tamoxifen-treated participants. Compared with nontreated participants, the tamoxifen-treated women had no differences in the activities of daily vision, visual acuity measurements, or other tests of visual function except for color screening. Intraretinal crystals (odds ratio [OR]=3.58, P=.178) and posterior subcapsular opacities (OR=4.03, P=.034) were more frequent in the tamoxifen-treated group. CONCLUSIONS: Women should have a thorough baseline ophthalmic evaluation within the first year of initiating tamoxifen therapy and receive appropriate follow-up evaluations.

An eyelash in the vitreous cavity without apparent etiology.

Intraocular eyelashes are an infrequent complication of trauma to the eye. Intraocular cilia have a variable prognosis ranging from acute inflammation to remaining dormant within the vitreous for several years. However, intraocular cilia in the anterior chamber have been associated with delayed inflammatory responses, while intravitreal cilia may cause rhegmatogenous retinal detachment. All cases reported in the literature to this point have been able to identify some history of trauma, be it acute or remote. In this report a case is described in which intravitreal cilia were not associated with a history of trauma.

Diabetic retinopathy. Preserving your patients' sight.

Diabetic retinopathy is a major cause of morbidity and the leading cause of legal blindness in working-age persons in the United States. Retinopathy affects both juvenile-onset and noninsulin dependent diabetics. Most visual loss occurs in patients because they are seen late in the course of their disease. Several clinical trials have aided in establishing recommended screening and referral guidelines for patients with diabetes mellitus. Treatment strategies based on clinical trials are reviewed as well as the importance of control of both hyperglycemia and hypertension. Ocular findings are illustrated and discussed. The primary care physician can substantially reduce the risk of blindness and visual impairment in diabetic patients by prompt recognition of the ocular findings and understanding the importance of timely ophthalmologic evaluation.

The detection and quantification of retinopathy using digital angiograms.

An algorithm is presented for the analysis and quantification of the vascular structures of the human retina. Information about retinal blood vessel morphology is used in grading the severity and progression of a number of diseases. These disease processes are typically followed over relatively long time courses, and subjective analysis of the sequential images dictates the appropriate therapy for these patients. In this research, retinal fluorescein angiograms are acquired digitally in a 1024x1024 16-b image format and are processed using an automated vessel tracking program to identify and quantitate stenotic and/or tortuous vessel segments. The algorithm relies on a matched filtering approach coupled with a priori knowledge about retinal vessel properties to automatically detect the vessel boundaries, track the midline of the vessel, and extract useful parameters of clinical interest. By modeling the vessel profile using Gaussian functions, improved estimates of vessel diameters are obtained over previous algorithms. An adaptive densitometric tracking technique based on local neighborhood information is also used to improve computational performance in regions where the vessel is relatively straight.

Prospective evaluation of the effect of pseudophakic cystoid macula edema on contrast sensitivity.

OBJECTIVE: To evaluate the effect of pseudophakic cystoid macular edema (PCME) on contrast sensitivity. DESIGN: Best-corrected visual acuity, fluorescein angiogram, and contrast sensitivity measurements were obtained before surgery and at 8 weeks and 8.5 months after surgery. Eyes were classified as having no PCME, transient PCME, or persistent PCME. PARTICIPANTS: The study population consisted of 31 consecutive patients undergoing extracapsular cataract extraction with posterior chamber intraocular lens implantation between September 1990 and March 1991. MAIN OUTCOME MEASUREMENTS: Outcomes were best-corrected visual acuity and contrast sensitivity. RESULTS: Analysis of variance showed a significant decrease for all spatial frequencies at 8 weeks (P < .005) and for higher frequencies at 8.5 months (P < .05) in both PCME groups and for higher frequencies at 8 weeks in the transient PCME group. CONCLUSION: Decrease in contrast sensitivity associated with PCME may account for persistent visual difficulties despite good Snellen visual acuity.

Microrips of the retinal pigment epithelium.

We describe six patients with exudative age-related macular degeneration who had retinal pigment epithelial detachments with associated overlying neurosensory detachments. During fluorescein angiography, each patient demonstrated a solitary, intense, central serouslike leak at the edge of the retinal pigment epithelial detachment with passage of fluorescein into the subretinal space. In patients in whom the location of associated choroidal neovascularization was evident, the leakage site was remote to the area of neovascularization. Our observations suggest that these leaks result from small retinal epithelial rips, which we termed "microrips," that differ from conventionally described retinal pigment epithelial rips in clinical course and response to laser treatment. We hypothesize that the mechanisms and forces that generate these microrips are different from those producing conventionally described retinal pigment epithelial rips.

Natural history of subfoveal pigment epithelial detachments associated with subfoveal or unidentifiable choroidal neovascularization complicating age-related macular degeneration.

There have been few studies of the natural history of pigment epithelial detachments associated with choroidal neovascularization, and none confined to subfoveal lesions. We studied the natural history of 55 eyes in 53 patients who had age-related macular degeneration and subfoveal pigment epithelial detachment associated with choroidal neovascularization that was subfoveal or unidentifiable in location. Life table analysis showed that, at 1-year follow-up, 65% had a visual acuity less than 20/200 and 26% had less than 5/200. Age was a significant risk factor for reduction in both initial and final visual acuity. The presence of both hemorrhage and exudate on initial presentation was a significant risk factor for poor initial visual acuity.

Tunable dye laser photocoagulation for choroidal neovascularization complicating age-related macular degeneration.

We report our first 146 consecutive eyes treated with tunable dye laser for choroidal neovascular membrane (NVM) complicating age-related macular degeneration (AMD). They were treated with the orange (595 nm; N = 6), red (630 nm; N = 23), yellow (577 nm; N = 67), or sequential red-yellow (N = 50) wavelength of the tunable dye laser. All had a minimum 180 days follow-up. Eyes were analyzed as two groups categorized by pretreatment visual acuity (VA): 20/100 or better (N = 101), and 20/200 or worse (N = 45). Change in VA between baseline and most recent follow-up was studied by age, laser color, previous non-dye laser treatment, and number of treatments. Age was a statistically significant variable (chi 2 = 6.61, degree of freedom = 2, P less than 0.05). In eyes with initial VA of 20/100 or better, age also was significant for cumulative percent loss in VA of greater than or equal to 2 lines. We discontinued using orange after poor early clinical results. Our results suggest that the dye laser's variety and combination of wavelengths may provide advantages in treating NVM complicating AMD.

Current management of choroidal neovascularization.

Age-related macular degeneration is the leading cause of blindness in Americans over age 65. In 1982, the Macular Photocoagulation Study (MPS) established that argon laser photocoagulation reduces the risk of severe visual loss in eyes with extrafoveal choroidal neovascularization (CNV) associated with macular degeneration. Subsequently, similar results were found for histoplasmic and idiopathic choroidal neovascularization. There are also encouraging data on photocoagulation of CNV in other diseases and with different wavelengths. The MPS Group has found the krypton laser to be effective for juxtafoveal CNV secondary to histoplasmosis and is evaluating argon green and krypton red lasers for subfoveal CNV. Other investigators are evaluating laser treatment of CNV associated with myopic degeneration, pigment epithelial detachment, and angioid streaks. The new tunable dye laser may further expand our ability to treat this disorder. Until CNV can be prevented, laser photocoagulation remains the treatment of choice, and clinical trials should identify appropriate cases.

Krypton laser for proliferative diabetic retinopathy: the Krypton Argon Regression of Neovascularization Study.

The Krypton Argon Regression of Neovascularization Study (KARNS) is a multicenter, randomized, controlled clinical trial designed to determine the efficacy of red krypton laser photocoagulation in the treatment of proliferative diabetic retinopathy.

Laser photocoagulation for choroidal new vessel membrane complicating age-related macular degeneration associated with pigment epithelial detachment.

We studied 124 consecutive eyes that had laser photocoagulation for choroidal new vessel membranes (NVM) associated with pigment epithelial detachment (PED). In many cases, the extent of the NVM was uncertain. We thought it was not subfoveal in all cases but it possibly may have been subfoveal in one subgroup of cases. With a mean follow-up of 16 months, vision was stable or improved in 53% of the treated eyes. There was no difference in outcome between argon-treated and krypton-treated eyes. On the basis of fluorescein angiograms, we classified 86 of the eyes into four nonexclusive groups. Vision was stable or improved in 68% of eyes with juxtafoveal or extrafoveal PED, 48% with subfoveal PED, 76% with juxtafoveal or extrafoveal NVM, and 50% of eyes with possibly subfoveal NVM. A randomized clinical trial of laser photocoagulation for NVM in PED is both indicated and warranted. A pilot study under the auspices of the Macular Photocoagulation Study is now under way to determine the feasibility of and develop a protocol for such a trial.

Vision loss in age-related maculopathy: primary care referral guide.

The primary care practitioner is frequently the first professional to whom the elderly patient will complain of blurred or distorted vision. The authors focus here on the leading cause of vision loss in the elderly--age-related macular degeneration (ARMD)--and the role of primary care in its detection and in referral for treatment. An overview of ARMD is presented, with discussion of pathophysiology, various forms of the disease, and available treatments. The importance of referral of these patients at the primary care level is noted. The authors also comment on patient education, low vision aids, and eye care for the disadvantaged.