Randomized trial of peribulbar triamcinolone acetonide with and without focal photocoagulation for mild diabetic macular edema: a pilot study.

OBJECTIVE: To provide pilot data on the safety and efficacy of anterior and posterior sub-Tenon injections of triamcinolone either alone or in combination with focal photocoagulation in the treatment of mild diabetic macular edema (DME). DESIGN: Prospective, phase II, multicenter, randomized clinical trial. PARTICIPANTS: One hundred nine patients (129 eyes) with mild DME and visual acuity 20/40 or better. METHODS: The participants were assigned randomly to receive either focal photocoagulation (n = 38), a 20-mg anterior sub-Tenon injection of triamcinolone (n = 23), a 20-mg anterior sub-Tenon injection followed by focal photocoagulation after 4 weeks (n = 25), a 40-mg posterior sub-Tenon injection of triamcinolone (n = 21), or a 40-mg posterior sub-Tenon injection followed by focal photocoagulation after 4 weeks (n = 22). Follow-up visits were performed at 4, 8, 17, and 34 weeks. MAIN OUTCOME MEASURES: Change in visual acuity and retinal thickness measured with optical coherence tomography (OCT). RESULTS: At baseline, mean visual acuity in the study eyes was 20/25 and mean OCT central subfield thickness was 328 mum. Changes in retinal thickening and in visual acuity were not significantly different among the 5 groups at 34 weeks (P = 0.46 and P = 0.94, respectively). There was a suggestion of a greater proportion of eyes having a central subfield thickness less than 250 mum at 17 weeks when the peribulbar triamcinolone was combined with focal photocoagulation. Elevated intraocular pressure and ptosis were adverse effects attributable to the injections. CONCLUSIONS: In cases of DME with good visual acuity, peribulbar triamcinolone, with or without focal photocoagulation, is unlikely to be of substantial benefit. Based on these results, a phase III trial to evaluate the benefit of these treatments for mild DME is not warranted.

North Carolina macular dystrophy (MCDR1) locus: a fine resolution genetic map and haplotype analysis.

PURPOSE: We previously reported linkage of North Carolina macular dystrophy in a single isolated family to a broad region on chromosome 6q16. In order to refine the localization of the MCDR1 gene (North Carolina macular dystrophy), additional families with this disease and new markers were studied. METHODS: We ascertained 10 families with the North Carolina macular dystrophy phenotype (MCDR1). These families were of various ethnic and geographic origins such as Caucasian, Mayan Indian, African-American, French, British, German, and American of European decent. Two hundred thirty-two individuals in these families underwent comprehensive ophthalmic examinations and blood was collected for genotyping. One hundred seventeen were found to be affected. Linkage simulation studies were performed. Two-point linkage, haplotype analysis, and multipoint linkage was performed using VITESSE and FASTLINK. HOMOG was used to test for genetic heterogeneity. RESULTS: The clinical features were consistent with the diagnosis of North Carolina macular dystrophy in all families. Multipoint linkage analysis indicates that the MCDR1 gene is in the interval between D6D249 and D6S1671 with a maximum LOD score of 41.52. There was no evidence of genetic heterogeneity among the families studied. Families 765, 768, 772, 1193, and 1292 shared the same chromosomal haplotype in this region. CONCLUSIONS: This is the largest single data set of families with the MCDR1 phenotype. The single large family from North Carolina continues to be informative for the closest flanking markers and alone supports the minimal candidate region as suggested by previous studies. There remains no evidence of genetic heterogeneity in this disease. Most of the American families appear to have descended from the same ancestral mutation. The remaining families could each represent independent origins of the mutation in the MCDR1 gene.

Prophylactic laser treatment to fellow eyes of unilateral retinal pigment epithelial tears.

PURPOSE: To evaluate prophylactic laser treatment of the macula in reducing the risk of visual loss in the fellow eye of patients with a retinal pigment epithelial tear caused by age-related macular degeneration in the first eye. METHODS: In a prospective study, 12 patients with a retinal pigment epithelial tear in one eye caused by age-related macular degeneration and drusen in the fellow eye received prophylactic laser treatment of the retina in their fellow eyes and were followed up for 2 years or more after prophylactic treatment. RESULTS: In 12 fellow eyes that received prophylactic laser treatment, a reduction in best-corrected visual acuity to 20/80 or worse occurred in one (8%) of 12 eyes in the first year and two (18%) of the remaining 11 eyes in the second year after treatment. The cumulative risk of visual loss in the treated fellow eye was 25% in 2 years. CONCLUSIONS: In historical control subjects in a natural history study of patients with retinal pigment epithelial tear in one eye, central visual loss occurred in 16 (37%) of 43 eyes in the first year and in seven (30%) of 23 eyes in the second year for a cumulative loss of 59% in the first 2 years. Compared with these historical control subjects, our findings suggest that visual loss in the fellow eyes of patients with a retinal pigment epithelial tear in the first eye is reduced by prophylactic low intensity laser photocoagulation of the macula.

Difference between RP2 and RP3 phenotypes in X linked retinitis pigmentosa.

AIM: X linked retinitis pigmentosa (XLRP) has two genetic loci known as "RP2" and "RP3". Clinical features reported to differentiate RP2 from RP3 include a higher prevalence of myopia and primary cone dysfunction in RP2, and late onset night blindness and tapetal reflex in RP3. Members from 14 XLRP families were examined in an attempt to verify these differences. METHODS: 16 affected males and 37 females from 14 XLRP families assigned as either RP2 or RP3 by haplotype analysis and/or by heterogeneity analysis were examined. Members of all 14 families who were willing to participate but unavailable for examination were contacted and detailed interviews carried out. RESULTS: No clear phenotypic differences were found that could be used to reliably differentiate RP2 from RP3 with respect to myopia and onset of night blindness. The tapetal reflex was also found to be present in carriers of both RP2 and RP3. CONCLUSIONS: XLRP is a heterogeneous class of rod degenerative disorders with no clear phenotypic differentiation between the two genetic loci RP2 and RP3. There is a continuum of clinical presentations which can be seen in both RP2 and RP3, but the features within a given family tend to be consistent. However, interfamilial variability is prevalent leading to a wide range of clinical presentations and more than one abnormal allele at each gene locus cannot be excluded.

Phacoemulsification and silicone oil removal through a single corneal incision.

OBJECTIVE: Cataracts are a frequent complication after silicone oil infusion for the repair of complicated retinal detachments, occurring in up to 100% of eyes retaining silicone oil for 6 months or more. The authors devised a combined procedure for cataract and silicone oil removal with intraocular lens (IOL) implantation through a single corneal incision and evaluated their results. DESIGN: A prospective, noncomparative case series. PARTICIPANTS: Thirty-four eyes of 34 consecutive patients with a history of retinal detachment repair requiring silicone oil placement in whom a clinically significant cataract subsequently developed were identified when removal of silicone oil was scheduled. INTERVENTION: All 34 eyes were prospectively entered into a study to evaluate the efficacy and potential complications of a combined procedure for cataract and silicone oil removal with posterior chamber lens implantation. All patients underwent uncomplicated phacoemulsification removal of cataract followed by removal of silicone oil and placement of an IOL through a single corneal incision. MAIN OUTCOME MEASURE: Recurrent retinal detachment and IOL-related complications were measured. RESULTS: Ten eyes had recurrent retinal detachments develop. Final visual acuity ranged from 6/12 to hand movements with 25 eyes (74%) showing stabilized or improved vision. Pre-existing macular pathology and recurrent retinal detachment generally were responsible for poor visual outcome. CONCLUSIONS: Combined phacoemulsification, IOL implant with silicone oil removal is a useful procedure in these complicated eyes. Visual outcome generally is good with improvement in visual acuity, even with recurrent retinal detachment or pre-existing macular pathology or both.

Visual outcome after silicone oil removal and recurrent retinal detachment repair.

PURPOSE: Prospective analysis of the effect of removal of silicone oil (ROSO) in eyes with complicated retinal detachments and evaluation of the visual outcome following recurrent retinal detachment after silicone oil removal. METHODS: We evaluated 62 consecutive cases of ROSO over a 12 month period. All eyes had previously undergone silicone oil placement for complicated retinal detachments. All eyes undergoing scheduled ROSO over the time period of the study were entered and were reviewed post-operatively. RESULTS: Sixty-two eyes were entered into the study. Twenty-one of 62 (34%) developed recurrent retinal detachment following ROSO; 18 of these 21 recurrent detachments were reattached with one additional procedure and only 5 required replacement of the silicone oil. Ten of these 21 eyes (48%) had improvement or stabilisation in final visual acuity compared with the presenting visual acuity. Overall, 39 eyes (63%) had improvement in vision following ROSO and 76% of all eyes had ambulatory visual acuity at the end of the follow-up period. Fourteen eyes required cataract extraction with ROSO to attain this final visual acuity. CONCLUSIONS: Overall, ROSO has a significant rate of recurrent retinal detachment, with a high reattachment rate with one additional procedure. Few of these eyes need the silicone oil replaced. Most eyes will retain ambulatory visual acuity even with multiple procedures in cases of complicated retinal detachments following ROSO even with recurrent retinal detachment.

Intraocular penetration of tamoxifen.

OBJECTIVE: To document ocular penetration of oral tamoxifen in patients being administered systemic therapy by measuring intraocular and serum levels of the drug in a series of patients undergoing elective ocular surgery. DESIGN: Nonrandomized, prospective, comparative trial. PARTICIPANTS: Twenty-one eyes of 21 patients undergoing elective ocular surgery (cataract extraction or vitrectomy). Twenty patients were using the antiestrogen, tamoxifen, and one participant was not. Nine patients were excluded in the final analysis because of inadequate sample size. INTERVENTION: Preoperative serum samples and perioperative aqueous samples, vitreous samples, or both were obtained for each patient, and these were analyzed for tamoxifen and its metabolites. Dilated fundus examination was performed before surgery on all patients. MAIN OUTCOME MEASURES: Evidence of tamoxifen, its metabolites, or both in the samples. RESULTS: Tamoxifen was detected in all analyzed serum samples (range, 82.4-290.0 ng/ml.) from patients taking the medication and was found to have penetrated into both vitreous (range, 0.5-7.8 ng/ml) and aqueous (range, 0.5-3.9 ng/ml) cavities. No relationship was found between serum and intraocular levels. CONCLUSIONS: This study shows that tamoxifen penetrates intraocular fluids to varying degrees. The drug levels in aqueous and vitreous do not appear to correlate with serum levels. Evidence of tamoxifen retinopathy or keratopathy was not seen.

Vitreoretinal surgery after inadvertent globe penetration during local ocular anesthesia.

OBJECTIVE: This study aimed to review visual morbidity resulting from inadvertent globe penetration during administration of local anesthetic and to identify the most appropriate management. DESIGN: The records of 20 consecutive patients referred to a specialist vitreoretinal unit over a 2-year period were reviewed. PARTICIPANTS: Twenty eyes of 20 consecutive patients were included. INTERVENTION: Observations included type of local anesthetic administered (e.g., retrobulbar or peribulbar), level of training of person administering the block, type of needle used for the block, and findings at presentation to the vitreoretinal unit. The authors also observed results of B-scan ultrasound evaluation of the retina, interval between the recognition of the complication and referral, as well as nature and timing of subsequent surgical intervention. MAIN OUTCOME MEASURES: Final visual acuity and retinal status (attached versus detached) were measured. RESULTS: The most common presentation was vitreous hemorrhage observed from the first postoperative day. Ten eyes were found to have an associated retinal detachment on initial assessment in the vitreoretinal unit. These eyes generally had a poor visual outcome despite vitrectomy with long-acting gas or silicone oil tamponade. Seven (70%) of the remaining eyes with attached retina at the time of presentation achieved good visual recovery after vitrectomy. CONCLUSIONS: The authors recommend prompt referral for consideration of early vitrectomy in eyes with dense vitreous hemorrhage after inadvertent globe penetration. This management may improve the overall visual prognosis by preventing subsequent retinal detachment.

The use of corticosteroids for choroidal neovascularisation in young patients.

PURPOSE: To investigate the role of systemic corticosteroids in the treatment of sight-threatening choroidal neovascularisation (CNV) in patients with punctate inner choroidopathy (PIC) and multifocal inner choroiditis (MIC). METHODS: Twelve eyes of 10 patients with evidence of PIC or MIC with recent visual symptoms were identified. All eyes had CNV within the foveal avascular zone on fundus fluorescein angiography (FFA). Systemic oral prednisolone at an initial dose of 1 mg/kg (60-80 mg) was given for 3-5 days and the dose was subsequently tapered. Changes in best corrected visual acuity and leakage on FFA were recorded during follow-up. Systemic side-effects of the corticosteroids were monitored. RESULTS: In 10 of 12 eyes vision improved or stabilised. Leakage on FFA resolved in 9 eyes and was reduced in 3. Four patients required more than one course of oral corticosteroids. One patient was maintained on low-dose oral corticosteroids for recurrent CNV activity. No systemic complications from the treatment were observed. CONCLUSION: A course of oral corticosteroids in healthy young patients with subfoveal CNV in PIC or MIC may reduce subretinal vascular leakage and stabilise vision when no other proven treatment option is available.

Partial laser ablation of massive peripapillary subretinal neovascularization.

BACKGROUND: Although peripapillary subretinal neovascular membranes (PSRNs) are less common and often larger than neovascular complexes arising near the fovea, they may lead to severe visual loss. Very large (massive) PSRNs (MPSRNs) are 3.5 disc areas or greater in overall size, are even less common, and may contain a significant occult component, leading to slow and unpredictable growth. Such massive lesions may begin at the nasal margin of the disc and do not become symptomatic until they have extended around the disc toward the macula, threatening central vision. Although complete laser ablation has been used for symptomatic PSRNs with variable success, the optimal treatment of MPSRNs remains controversial. METHODS: The authors reviewed the clinical course of 12 eyes of seven patients with MPSRNs. Ten eyes received laser treatment, which was limited to the temporal portion of the subretinal neovascular complexes only and two received no treatment. RESULTS: Of the ten eyes receiving laser treatment, six showed stabilization of visual acuity, whereas in four the neovascular membrane progressed beneath the fovea with severe visual loss. In the two untreated eyes, the subretinal neovascular membrane progressed beneath the macula with the loss of central vision. CONCLUSIONS: In contrast to the small symptomatic PSRNs, which are usually treated by complete laser ablation, MPSRNs may stabilize with only partial laser treatment. However, both types of lesions may remain stable for long periods of time without any treatment and require treatment only if progression toward the fovea occurs.

Peripheral transscleral retinal diode laser for rubeosis iridis.

PURPOSE: To evaluate the results of peripheral transscleral retinal diode photocoagulation with or without transscleral cyclodiode therapy in patients with rubeosis iridis with or without elevated intraocular pressure and no fundal view. METHODS: Peripheral transscleral retinal diode photocoagulation was performed in 15 eyes of 13 patients in an attempt to promote regression of rubeosis. The fundus could not be seen in any of the 15 eyes, so conventional panretinal photocoagulation was not possible. Nine eyes had associated elevated intraocular pressure and were treated with concurrent transscleral diode cyclophotocoagulation. RESULTS: All eyes showed regression of rubeosis. Of the nine eyes treated with combination therapy, six had stabilized intraocular pressure, and three developed hypotony. None of the eyes developed a peripheral retinal detachment, and one eye lost the ability to perceive light. CONCLUSIONS: This method is effective in treating patients with rubeosis iridis when the view of the fundus is inadequate for conventional panretinal photocoagulation and more extensive intraocular surgery is precluded. It may be combined with transscleral cyclophotocoagulation therapy to manage concurrent high intraocular pressure in rubeotic glaucoma, but this involves a risk of postoperative hypotony.

Scleral rupture during retinal detachment surgery: risk factors, management options, and outcomes.

OBJECTIVE: To evaluate the potential risk factors, management strategies, and outcomes of scleral rupture during retinal detachment (RD) surgery. DESIGN: Case-control study. PARTICIPANTS AND CONTROLS: Fourteen consecutive patients with scleral rupture during RD surgery (cases) and 65 consecutive patients who underwent RD surgery without scleral rupture (controls). INTERVENTION: Demographic and clinical data were abstracted from patients' medical records. OUTCOME MEASURES: Visual acuity and retinal attachment status at the last examination. RESULTS: Significant risk factors for scleral rupture during RD surgery were reoperation after failed RD surgery (71 % vs. 32%), and pre-existing scleral pathologic condition (29% vs. none). The site of rupture was in the bed of a previously placed scleral buckle in all patients with a previous buckling surgery. Repair of the rupture included scleral sutures in eight (57%), scleral patch graft in four (29%), and placement of a scleral buckle over the site in two (14%) eyes. Eleven (79%) underwent vitrectomy with retinal tamponade by gas (n = 4) or silicone oil (n = 7). Complications observed postoperatively included vitreoretinal incarceration (n = 3), vitreous hemorrhage (n = 2), suprachoroidal hemorrhage (n = 2) and subretinal hemorrhage (n = 3). In the 14 eyes with scleral rupture, the final visual acuity was > or =20/40 in 1 (7%), 20/50 to 20/200 in 5 (36%), and <20/200 in 8 (57%). Ten (71 %) had proliferative vitreoretinopathy develop. The retina was attached in 7 (50%), 6 (43%) had localized peripheral detachment, and 1 had a total retinal detachment. The vision improved in 4 (29%), was unchanged in 5 (36%), and was worse than before surgery in 5 (36%). In the 65 controls, the visual acuity at the time of the last examination was > or =20/40 in 26 (40%), 20/50 to 20/200 in 21 (32%), and <20/200 in 18 (28%). Sixty three (97%) patients had complete retinal reattachment, 1 (2%) had a localized peripheral RD, and 1 (2%) had an RD involving the posterior pole. After surgery, the vision improved in 45 (69%), was unchanged in 15 (23%), and was worse in 5 (8%) of the control eyes. The visual and anatomic outcomes of the eyes with scleral rupture were significantly worse than in the control group (P = 0.002 and P < 0.001, respectively). CONCLUSIONS: Risk factors associated with intraoperative scleral rupture include reoperation for failed RD surgery and pre-existing scleral pathology. Although this complication may be compatible with a good visual outcome in some patients, a high incidence of persistent or recurrent RD with proliferative vitreoretinopathy worsens the visual outcome for most patients with this complication.

Proton beam irradiation of subfoveal choroidal neovascularisation in age-related macular degeneration.

PURPOSE: To assess the safety and potential toxicity of proton beam radiation in the treatment of subfoveal choroidal neovascular membrane (CNVM) due to age-related manner degeneration (ARMD) in a prospective, non-randomised study. METHODS: Forty-eight eyes of 46 consecutive patients with subfoveal CNVM due to ARMD, not amenable to laser photocoagulation, were treated prospectively with a single proton beam exposure. Two dose regimens were evaluated: 8 CGE (Cobalt Gray Equivalent) and 14 CGE. Patients were followed for an average of 22.1 months after proton beam treatment. RESULTS: At the 12 month follow-up, 44% of eyes in the 8 CGE group and 75% of the eyes in the 14 CGE group had stabilized or improved visual acuity. Complex size in the 8 CGE group as measured on standard fluorescein angiography (FA), decreased or had no change initially but showed less effect over time, while the eyes treated with 14 CGE maintained decreased leakage over the follow-up period of 12 months. However, 11 eyes in the 14 CGE group experienced radiation retinopathy, with the onset between 3 and 30 months. Seven of these 11 eyes have demonstrated some visual loss but only 1 eye developed severe visual loss at 15 months after proton treatment. CONCLUSIONS: To date, 14 CGE has suggested a favourable influence on visual function and growth inhibition of CNVM. Proton beam irradiation appears to inhibit CNVM growth. The 14 CGE dose regimen appears to have a longer effect of CNVM growth than does 8 CGE, with overall stabilisation of visual function and growth inhibition. Radiation retinopathy has developed over time, but severe visual loss has been limited. On the basis of the incidence of radiation retinopathy, adjustments in the total radiation dosage and/or fractionation of the dosage should be considered.

Treatment of pigment epithelial detachments due to age-related macular degeneration with intra-ocular C3F8 injection.

PURPOSE: To flatten pigment epithelial detachments (PED) due to age-related macular degeneration in an attempt to visualize the underlying choroidal neovascularization by fluorescein angiography (FA) and reveal a treatment target. METHODS: Nine patients with PED received intravitreal gas injections via the pars plana and postured face down. Fluorescein angiograms were obtained before and after gas injection. In two patients, retinal scotopic sensitivity was also measured. RESULTS: Eight patients demonstrated change in the shape and size of the PED following gas injection. Four patients showed a better delineation of underlying structures on FA. Three patients had focal laser treatment to the newly visible choroidal neovascular complex, but this was successful in only one patient with flattening of the PED. CONCLUSION: Pigment epithelial detachments can be modified by intravitreal gas injection in some patients, but this treatment did not have a major impact on overall outcome or management.