Christina J. Flaxel

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 stabilised 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.

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.Conclusion 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.

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.

Prophylactic Treatment of Age-Related Macular Degeneration Report Number 2: 810-Nanometer Laser to Eyes With Drusen: Bilaterally Eligible Patients

BACKGROUND AND OBJECTIVEnTo determine the prophylactic and therapeutic value of a single subthreshold 810-nanometer laser treatment in patients with high risk drusen as a manifestation of dry age-related macular degeneration in both eyes.nnnPATIENTS AND METHODSnThe Prophylactic Treatment of Age-related Macular Degeneration study enrolled 1,278 eyes of 639 participants who were 50 years or older with at least 5 drusen 63 microm or more in diameter in each eye. Treatment consisted of the placement of an annular grid of 48 extrafoveal, subthreshold 810-nm diode laser applications centered at but sparing the foveola in one eye of each participant, with the fellow eye serving as a control. Development of choroidal neovascularization and change in best-corrected visual acuity were compared between treated and untreated eyes.nnnRESULTSnSubthreshold laser treatment did not decrease the incidence of choroidal neovascularization in treated versus untreated eyes. A modest visual acuity benefit in treated eyes was found at 24 months (1.5 letter difference; P = .04) and in the treated eyes of participants with a baseline visual acuity between 20/32 and 20/63 (4.0 letter difference; P = .0034). However, this treatment effect was not sustained at 3 years.nnnCONCLUSIONnA single subthreshold 810-nanometer laser treatment to eyes of participants with bilateral high risk drusen is not an effective prophylactic strategy against choroidal neovascularization.

Effect of a novel octapeptide urokinase fragment, A°6, on experimental choroidal neovascularization in the monkey

Purpose: To evaluate the inhibitory effects of a urokinase-derived octapeptide, A˚6, on laser-induced choroidal neovascularization (CNV) in monkeys. Methods: Twenty female cynomolgus monkeys were randomly grouped into weekly or monthly A˚6 treatment groups, each consisting of 10 animals. CNV was induced in both eyes by perimacular laser treatment. In each right eye, a single 22.25-mg A˚6 dose (monthly group) or 4 22.25-mg A˚6 doses each week (weekly group) were given by intravitreal injections. Each left eye received phosphate buffer on the same schedule. Monkeys were observed for 4 weeks by ophthalmic examinations, color photography, and fluorescein angiography. Results: Weekly treated eyes had a 35% reduction of CNV compared with controls (P = 0.23). In contrast, monthly treated eye had a 71% reduction of CNV compared with controls (P = 0.0009). There was no evidence of toxicity at both clinical and pathologic examinations. Conclusions: Intravitreal A˚6 injections effectively inhibited CNV in cynomolgus monkeys without evidence of toxicity. The overall reduction in CNV was greater for monthly treated eyes than for weekly treated eyes. This study suggests that A˚6 has promise as a local antiangiogenic treatment of CNV. Further work is indicated to evaluate the potential role of A˚6 in therapy for human CNV associated with age-related macular degeneration.

Use of radiation in the treatment of age-related macular degeneration

In this century, macular degeneration is likely to reach epidemic proportions. New treatment modalities are being evaluated for wet or neovascular age-related macular degeneration (AMD) and include radiation treatment. Radiation is known to potentially destroy vascular tissue, and low-dose radiation has been shown to inhibit new blood vessel growth. Potential advantages to radiation therapy in treating AMD include the absence of iatrogenic mechanical or laser damage, the absence of systemic side effects, and the absence of local side effects caused by periocular and intraocular injection. An additional advantage is that eyes with primarily large, occult choroidal neovascularization are potentially eligible for treatment, and only one treatment would be necessary. The major potential side effect is radiation retinopathy, which is dose dependent.

One-year results of a pilot study using oral 13-cis retinoic acid as a treatment for subfoveal predominantly occult choroidal neovascularization in patients with age-related macular degeneration.

Purpose: To evaluate the safety and evidence of efficacy for oral 13-cis retinoic acid as a treatment for patients with subfoveal occult choroidal neovascularization (CNV) due to age-related macular degeneration (ARMD). Methods: Patients with active, subfoveal occult CNV with no prior treatment of the subfoveal component were eligible for inclusion. Patients received 40 mg of 13-cis retinoic acid twice daily for 5 months, stopped treatment for 2 months, and then resumed treatment for 5 months. Patients were observed monthly with Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA), clinical examination, fluorescein angiography, and laboratory testing. Results: Eleven patients, aged 64 to 88 years, were enrolled and followed for 1 year. Initial VA ranged from 55 (20/40) to 5 (20/400) ETDRS letters (median 48 letters). Mild drug-related side effects (dry skin, chapped lips) occurred in all 11 patients. Three patients experienced more severe side effects (muscle aches, mood swings) and did not resume treatment after the drug holiday. Moderate VA loss occurred in 36% at both 6 and 12 months. Conclusions: Oral 13-cis retinoic acid is too toxic to be useful in patients with ARMD. Oral 13-cis retinoic acid did not improve vision although it may have slowed visual acuity loss in patients with ARMD with occult subfoveal CNV.

Oxygen saturation in premature infants at risk for threshold retinopathy of prematurity.

Purpose We aimed to determine if oxygen saturation, desaturations, and saturation variability play a role in progression of retinopathy of prematurity (ROP) and need for laser treatment. Methods This was a retrospective case-control study. We performed chart review of premature infants in a university hospital neonatal intensive care unit consecutively examined for ROP between May 2000 and December 2001. We compared birthweight, postmenstrual age, and oxygen saturation for 3 weeks before laser treatment for threshold ROP in group 1 (n=19) (average weight at treatment 2508 grams) and group 2 (n=18) before they reached 2500 grams. Outcome measures were retinopathy progression and need for treatment. Results Adjusting for birthweight and postmenstrual age, known predictors of ROP progression, we found that babies requiring laser treatment (group 1) had lower average daily oxygen saturation levels in the study period, significantly on 5/20 days (25%). These babies had saturations below 95% on 18/20 days (90%). Babies not requiring laser (group 2) had saturations below 95% on 2/20 days (10%). The last day on which pretreatment saturations differed significantly was 2 days before laser. Group 1 had more desaturations below 80% (6.0±3.2) than group 2 (3.2±1.2), p=0.0002 (independent samples t tests). Saturations varied more for individual group 1 infants. Conclusions Decreased oxygen saturation as early as 3 weeks and as late as 2 days before laser, increased number of desaturations, and saturation variability were seen in babies eventually requiring laser treatment for ROP.