John R. Gonder

Long-term Benefit of Sustained-Delivery Fluocinolone Acetonide Vitreous Inserts for Diabetic Macular Edema

OBJECTIVE To assess the efficacy and safety of intravitreal inserts releasing 0.2 μg/day (low dose) or 0.5 μg/day (high dose) fluocinolone acetonide (FA) in patients with diabetic macular edema (DME). DESIGN Two parallel, prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trials. PARTICIPANTS Subjects with persistent DME despite at least 1 macular laser treatment were randomized 1:2:2 to sham injection (n = 185), low-dose insert (n = 375), or high-dose insert (n = 393). METHODS Subjects received study drug or sham injection at baseline and after 6 weeks were eligible for rescue laser. Based on retreatment criteria, additional study drug or sham injections could be given after 1 year. MAIN OUTCOME MEASURES The primary outcome was the percentage of patients with improvement from baseline best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Trial (ETDRS) letter score of 15 or more at month 24. Secondary outcomes included other parameters of visual function and foveal thickness (FTH). RESULTS The percentage of patients with improvement from baseline ETDRS letter score of 15 or more at month 24 was 28.7 and 28.6 in the low- and high-dose insert groups, respectively, compared with 16.2 in the sham group (P = 0.002 for each). Benefit occurred for both doses compared with sham at 3 weeks and all subsequent time points. The mean improvement in BCVA letter score between baseline and month 24 was 4.4 and 5.4 in the low- and high-dose groups, respectively, compared with 1.7 in the sham group (P = 0.02 and P = 0.016). At all time points compared with sham, there was significantly more improvement in FTH. Subjects requiring cataract surgery were more frequent in the insert groups, and their visual benefit was similar to that of subjects who were pseudophakic at baseline. Glaucoma requiring incisional surgery occurred in 3.7%, 7.6%, and 0.5% of the low-dose, high-dose, and sham groups, respectively. CONCLUSIONS Both low- and high-dose FA inserts significantly improved BCVA in patients with DME over 2 years, and the risk-to-benefit ratio was superior for the low-dose insert. This is the first pharmacologic treatment that can be administered by an outpatient injection to provide substantial benefit in patients with DME for at least 2 years.

Uveal Malignant Melanoma Associated with Ocular and Oculodermal Melanocytosis

Seventeen patients with ocular or oculodermal melanocytosis were identified among 1,250 Caucasian patients with uveal malignant melanoma. The uveal melanomas in these seventeen patients were similar in size, cell type, and tendency to metastasize to those occurring in reported populations without ocular or oculodermal melanocytosis. Clinical and histopathologic study of these 17 cases indicated that all of the affected eyes had episcleral and choroidal melanocytosis and that other ocular and periocular tissues (sclera, iris, conjunctiva, angle structures, and optic disc) were involved less commonly. The uveal malignant melanoma that was present in each of these cases involved the eye with melanocytosis. Furthermore, the melanoma arose from the zone of uveal melanocytosis in every eye with sectoral involvement. Statistical analysis of these data supports the contention that uveal malignant melanoma has a higher incidence in white persons with ocular or oculodermal melanocytosis than in those without these conditions.

Ocular Melanocytosis: A Study to Determine the Prevalence Rate of Ocular Melanocytosis

A cross-sectional study was undertaken to determine the prevalence of ocular and oculodermal melanocytosis. Thirteen thousand one hundred fifty patients were examined for ocular and oculodermal melanocytosis. Fifty-three percent of these patients were black, 40% were white, and 7% were of other racial groups. In the white population, the prevalence of ocular melanocytosis was determined to be 0.038% (2/5251). In the black population, the prevalence of oculodermal melanocytosis was 0.014% (1/6915).

Growth rates and doubling times of posterior uveal melanomas.

Seventeen patients having a posterior uveal melanoma underwent enucleation following documentation of tumor growth. Duration of follow-up from diagnosis to enucleation ranged from 3 weeks to 30 months. The mean rate of enlargement in cubic tumor volume was 56.3 mm3/mo for eight spindle cell melanomas and 270.3 mm3/mo for nine mixed cell melanomas. The mean tumor doubling time calculated according to the exponential growth equation was 291.6 days for the eight spindle cell melanomas and 128.2 days for the nine mixed cell melanomas. The mean mitotic activity was 3.5 mf/40 hpf for the eight spindle cell melanomas and 5.4 mf/40 hpf for the nine mixed cell melanomas. These results suggest that mixed cell posterior uveal melanomas generally grow faster and have shorter doubling times than do spindle cell melanomas.

Comparison of the In vitro Safety of Intraocular Dyes Using Two Retinal Cell Lines: A Focus on Brilliant Blue G and Indocyanine Green

PURPOSE To compare the in vitro toxicity of brilliant blue G (BBG), indocyanine green (ICG), Trypan blue (TB), and Evans blue (EB) in a human retinal pigment epithelial cell line (ARPE-19) and a murine retinal ganglion/Muller glial (RGC) primary cell culture. DESIGN In vitro cell biology experimental study. METHODS The dose-dependent toxicity of the dyes was determined by exposing each dye at four different concentrations to the two cell cultures for a short exposure (three minutes) and a medium exposure (30 minutes). The time-dependent toxicity of the dyes was also determined. All four dyes, each diluted to 1/500th of stock concentration, were applied only to the ARPE-19 cells for a prolonged exposure of two, 24, 48, and 72 hours. Cell viability was measured via a mitochondrial dehydrogenase assay. RESULTS BBG was the only dye to cause toxicity in the ARPE-19 cell line at short exposure times. BBG and TB demonstrated toxicity at medium exposure times. BBG and ICG demonstrated toxicity at long exposure times and dilute concentrations. At short exposure times, none of the dyes caused toxicity in the RGC mixed primary cultures. In contrast, at medium exposure times, all dyes except ICG demonstrated toxicity that lessened with lower concentrations. CONCLUSIONS All dyes demonstrated relatively safe viability profiles in both cell lines at surgically relevant concentrations and times. Cell toxicity could be elicited at higher concentrations and longer exposure times. ICG had a favorable viability profile at almost all of the concentrations and times tested.

3. Intraocular Reticulum Cell Sarcoma

Abstract Reticulum cell sarcoma is a form of malignant lymphoma that may arise systemically in the reticuloendothelial cells of the spleen or lymph nodes, or in the microglial cells of the brain. Intraocular reticulum cell sarcoma occurs most frequently in association with central nervous system reticulum cell sarcoma. Although relatively uncommon, this diagnosis should be considered in any adult patient with vitreitis or chorioretinitis of unknown etiology, particularly if the inflammation does not respond to the usual therapy. The diagnosis of reticulum cell sarcoma must be considered with any uveitis or vitreitis associated with neurologic symptoms. Prompt diagnosis is of importance because the tumor is radiosensitive, and improved visual acuity and survival may follow radiation therapy.

OCULAR MANIFESTATIONS OF RELAPSING POLYCHONDRITIS

The clinical, ultrasonographic, fluorescein angiographic, and immunological features of a case of relapsing polychondritis in a 46-year-old female are described. Acute bilateral sclerouveitis with multiple retinal pigment epithelial defects and sensory retinal detachment were present on initial examination. Antibodies to type II collagen were present in serum samples taken from the patient during the acute and convalescent phase of the disease. A possible relationship of this disorder to the phylogenetic development of the eye is discussed.

Malignant Melanoma of the Choroid Associated with Oculodermal Melanocytosis

Abstract A 66-year-old white woman with oculodermal melanocytosis developed a malignant melanoma of the choroid in the right eye. The association of uveal melanoma with ocular and oculodermal melanocytosis is discussed. A differential diagnosis of ocular and oculodermal melanocytosis with emphasis on primary acquired melanosis is presented. Accurate diagnosis of ocular and oculodermal melanocytosis is important as these conditions have been reported to develop malignant melanoma of the skin, uveal tract, orbit, meninges, and brain.

Osteosarcoma in a Phthisical Feline Eye

Eight years ago a cat sustained injury to the left globe and phthisis bulbi ensued. Two months prior to presentation, a firm intraorbital and periorbital mass developed and enucleation was done; histologic examination revealed osteogenic sarcoma. This is the first histologically documented report of osteosarcoma occurring in association with phthisis bulbi.

Cystoid macular edema following combined phacoemulsification and vitrectomy for macular hole.

Purpose: To evaluate the incidence of cystoid macular edema (CME) in patients under‐going either combined or consecutive pars plana vitrectomy (PPV) and phacoemulsifica‐tion (PE) for the treatment of macular hole and cataract. Methods: Retrospective review of a consecutive surgical series of 22 patients with idiopathic macular holes. Seven patients underwent combined PPV with air‐fluid‐C3F8 gas exchange and PE with intraocular lens insertion; 15 patients underwent PE subsequent to PPV. Results: Visual acuity improved by 2 or more lines in 3/7 patients in the combined group and in 15/15 in the consecutive group. Of seven patients in the combined group, two required a second PPV for treatment of the macular hole and one declined further treatment. Of importance, 3/7 in the combined group and 1/15 in the consecutive group developed clinical and angiographic CME, all treated successfully with sub‐Tenon’s triamcinolone injections. Conclusions: Both combined PPV/PE and consecutive PPV/PE offer excellent potential therapeutic benefits for the treatment of idiopathic macular holes. The incidence and pathogenesis of CME must be further investigated.