Daniel P. Joseph

Outcome results in macular hole surgery: An evaluation of internal limiting membrane peeling with and without indocyanine green

PURPOSE To evaluate the anatomic closure rate and visual outcome in patients undergoing pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling with and without indocyanine green (ICG) enhancement. DESIGN Retrospective, noncomparative interventional case series. PARTICIPANTS One hundred ninety-three consecutive patients (204 eyes) seen at the Barnes Retina Institute with the clinical diagnosis of macular hole who underwent PPV between January 1998 and December 2000. INTERVENTION A consecutive series of 97 patients undergoing PPV with or without unilateral epiretinal membrane removal without ILM peeling (group 1), 44 patients with PPV and ILM peeling without ICG (group 2), and 35 patients with ICG-assisted ILM peeling (group 3). RESULTS Overall, 86.4% of the holes closed with one operation, with 75 of 97 (77.3%) eyes in group 1, 43 of 44 (97.7%) eyes in group 2, and 34 of 35 (97.1%) eyes in group 3 (chi(2)= 10.51, P = 0.007). Of the eyes that did not close, 18 patients in group 1 underwent repeat surgery, with 90 of 97 (92.8%) eyes ultimately achieving closure. Visual acuity after surgery was 20/50 or better in 55 of 97 (56.7%) patients, 31 of 44 (70.4%) patients, and 18 of 35 (51.4%) patients in groups 1, 2, and 3, respectively (chi(2) = 3.43, P = 0.18) and increased by 2 or more lines from their preoperative status in 63 of 97 (64.9%) patients, 34 of 44 (77.3%) patients, and 25 of 35 (71.4%) patients, respectively (chi(2)= 2.25, P = 0.32). Multivariate logistic regression demonstrated that use of ILM peeling during vitrectomy increases the chances of developing 20/50 vision or better (odds ratio [OR], 2.4; 95% confidence interval, 1.06-5.45; P = 0.04). No eyes received concurrent cataract extraction with macular hole surgery, but 75 of 166 (45.2%) required cataract extraction postoperatively. Complications included 20 retinal tears, 4 retinal detachments, and 34 patients with postoperative elevations in intraocular pressure (IOP; defined as IOP greater than 30 mmHg). CONCLUSIONS Although this study is limited by the shorter follow-up in patients undergoing ILM peeling with or without ICG relative to the control group, our experience indicates that the use of ILM peeling is associated with a statistically significant improvement in the rate of primary macular hole closure with a single operation.

Intravitreal Bevacizumab for Choroidal Neovascularization in Ocular Histoplasmosis

PURPOSE To define the role of intravitreal bevacizumab in individuals with choroidal neovascularization (CNV) resulting from Ocular Histoplasmosis syndrome (OHS). DESIGN Retrospective chart review of a surgical therapy. METHODS We reviewed the course of 28 eyes of 28 patients who underwent intravitreal injection of bevacizumab for treatment of CNV secondary to OHS. Outcome was measured by pretreatment and posttreatment visual acuity (VA). RESULTS The average pretreatment logarithm of the minimum angle of resolution (logMAR) VA was 0.65 (Snellen equivalent of 20/88). Mean follow-up was 22.43 weeks with an average of 1.8 intravitreal injections. Average final logMAR VA was 0.43 (Snellen equivalent of 20/54). Twenty eyes (71%) experienced an increase in central VA, whereas four eyes (14%) were unchanged and four eyes (14%) experienced a decrease in vision. CONCLUSIONS Intravitreal bevacizumab may improve or stabilize VA in a significant majority of patients with neovascular complications of OHS (24 eyes [85.7%] in our study population).

Ocular photodynamic therapy with verteporfin for choroidal neovascularization secondary to ocular histoplasmosis syndrome.

Purpose: To evaluate the use of ocular photodynamic therapy (OPT) with verteporfin in patients with choroidal neovascularization (CNV) from ocular histoplasmosis syndrome (OHS) and to compare these results with those for a natural history group. Methods: A retrospective chart review was performed to identify cases of CNV secondary to OHS treated with OPT. Complete data were available for 38 of 41 eligible eyes. Data regarding the following variables were abstracted from the patient charts: demographic characteristics, previous surgery, angiographic features, number and timing of treatments with OPT, follow‐up time, and visual acuity. The visual acuity results of eyes receiving photodynamic therapy were compared with those for a natural history cohort. Results: On average, OHS patients who received treatment developed 0.88 line of visual improvement. Visual acuity improved or stayed the same in 69% (22 of 32) of eyes, improved by ≥2 lines in 44% (14 of 32), and improved by ≥4 lines in 22% (7 of 32). Patients who received OPT were 2.07 times more likely to have improved or constant vision than were those in the natural history group as described in one retrospective series (odds ratio = 2.07; 95% confidence interval, 0.78‐5.56; P = 0.162). Thirty‐eight percent (12 of 32) of eyes had undergone submacular surgery for CNV before any OPT. Conclusions: Ocular photodynamic therapy with verteporfin may be beneficial in patients with CNV secondary to OHS, even in the setting of previous submacular surgery.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Cerebroretinal vasculopathy, hereditary vascular retinopathy, and hereditary endotheliopathy, retinopathy, nephropathy and stroke are neurovascular syndromes initially described as distinct entities. Recently they were shown to be one disease caused by C-terminal frame-shift mutations in TREX1 , which was termed ‘retinal vasculopathy with cerebral leukodystrophy’. Here we defined the genetic and clinicopathologic spectrum of this clinically and pathophysiologically poorly characterized and frequently misdiagnosed fatal neurovascular disorder. We identified five different TREX1 mutations in 78 members from 11 unrelated families and by using a standardized study protocol we retrospectively reviewed and aggregated the associated clinical, neuroimaging, and pathology data. Findings were similar across mutations and families. Sixty-four mutation carriers had vascular retinopathy. Neuroimaging revealed (i) punctate, hyperintense, white matter lesions with or without nodular enhancement in 97% of them; (ii) rim-enhancing mass lesions in 84%; and (iii) calcifications in the white matter in 52%. Ninety per cent had clinical manifestations of brain disease, including focal neurological deficits (68%), migraine (59%), cognitive impairment (56%), psychiatric disturbances (42%), and seizures (17%). One mutation carrier had enhancing brain lesions and neurological features but unknown retinopathy status. Additional systemic features included liver disease (78%), anaemia (74%), nephropathy (61%), hypertension (60%), mild Raynaud’s phenomenon (40%), and gastro-intestinal bleeding (27%). Mean (± standard deviation) age at diagnosis was 42.9 ± 8.3 years and at death 53.1 ± 9.6 years. Pathological examination revealed systemic vasculopathy with luminal narrowing and multi-laminated basement membranes. The 13 mutation carriers without retinopathy or brain lesions were on average 8 years younger (mean age: 35.1 ± 10.6 years). Of them, 54% had mild Raynaud’s phenomenon, 42% had migraine, and 23% had psychiatric disturbances. Retinal vasculopathy with cerebral leukodystrophy is an autosomal dominant systemic small-vessel disease due to specific TREX1 mutations and clinically primarily characterized by (i) visual impairment from vascular retinopathy; and (ii) neurological decline and premature death due to progressive enhancing cerebral white matter lesions. Impaired liver and kidney function, anaemia sometimes associated with gastrointestinal bleeding, hypertension, migraine, and Raynaud’s phenomenon appear to be part of the clinical spectrum as well. Penetrance seems high. Because of the pathogenetic basis and the emerging clinical picture with systemic manifestations and conspicuous absence of leukodystrophy, we renamed the disease ‘retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations’. We propose diagnostic criteria to facilitate clinical recognition and future studies. * Abbreviations : AGS : Aicardi-Goutieres syndrome MC : mutation carrier RVCL(-S) : retinal vasculopathy with cerebral leukoencephalopathy (and systemic manifestations)

Subretinal surgery for juxtafoveal choroidal neovascularization

Purpose To report visual outcome, rate of recurrence, and complications for patients who underwent subretinal surgery as treatment of classic juxtafoveal choroidal neovascularization (CNV). Methods This study was a noncomparative case series of 46 patients who underwent subretinal surgery for juxtafoveal CNV that appeared to be pure classic without angiographic or clinical evidence of occult neovascularization between 1993 and 2000, with best-corrected preoperative and postoperative Snellen visual acuity reported. Results The mean follow-up period ± SD was 20.4 ± 12.9 months (range, 6–57 months). Etiologic categories included ocular histoplasmosis syndrome (37%), age-related macular degeneration (20%), idiopathic (15%), myopic degeneration (11%), mixed features of ocular histoplasmosis syndrome and myopia (11%), and other miscellaneous causes (6%). Thirty-three percent (15) of 46 eyes that underwent surgery had previously been treated with thermal laser photocoagulation at least once. Most patients (89%) had membranes with the posterior edge located 200 &mgr;m or closer to the center of the foveal avascular zone. The median preoperative visual acuity was 20/70 compared with the median postoperative visual acuity of 20/40. Significant improvement of visual acuity, measured as an increase of two or more lines of vision, occurred in 26 eyes (56%). In 10 (22%) of the remaining eyes, postoperative visual acuity was within one line of the preoperative visual acuity. Visual acuity decreased by two to five lines in seven eyes (15%). Severe vision loss, defined as a decrease of six or more lines, occurred in three eyes (7%). Recurrence was observed in 26 patients (56.5%). Conclusion The results indicated that subretinal surgery for juxtafoveal CNV improved or stabilized vision in most cases (78%), but in the absence of controls with a limited number of eyes and variable follow-up, it is impossible to determine with certainty if this improvement or stabilization is greater than what might be seen with laser photocoagulation or observation.

Bevacizumab Versus Ranibizumab in the Treatment of Macular Edema Due to Retinal Vein Occlusion: 6-Month Results of the CRAVE Study.

BACKGROUND AND OBJECTIVE To compare efficacy of monthly treatment with bevacizumab or ranibizumab for macular edema due to retinal vein occlusion. PATIENTS AND METHODS Randomized, multicenter, comparative trial (ClinicalTrials.gov identifier: NCT01428388). Participants were randomized 1:1 to receive monthly treatment with bevacizumab or ranibizumab. The primary outcome was change in central foveal thickness at 6 months compared to baseline. RESULTS The trial randomized 98 patients to treatment with bevacizumab or ranibizumab. At 6 months, there were no differences in change in central foveal thickness between groups (bevacizumab: mean reduction of 212.6 µm, 95% confidence interval [CI], -288.3 to -137.0; ranibizumab: mean reduction of 243.8 µm, 95% CI, -309.6 to -178.0; P=.72, analysis of variance [ANOVA]). Both groups showed similar functional outcomes (bevacizumab: 0.33 logMAR gain, 95% CI, -0.47 to -0.18; ranibizumab: 0.34 logMAR gain, 95% CI, -0.45 to -0.23; P=.38, ANOVA). CONCLUSION In the treatment of retinal vein occlusion, bevacizumab and ranibizumab have similar effects on reducing macular thickness and improving visual acuity.

Treatment of neovascular age-related macular degeneration: past, present and future directions.

Purpose of review The treatment options of choroidal neovascularization due to age-related macular degeneration have expanded. Prior to ocular photodynamic therapy the only available treatment was laser photocoagulation. Clinicians and patients were not particularly enthusiastic despite its ability to stabilize vision. The purpose of the review is to review the past and current concepts of neovascular age-related macular degeneration therapy and to provide a short overview of upcoming treatments. Recent findings Photodynamic therapy provided us with the first realistic means to address subfoveal choroidal neovascularization lesions from age-related macular degeneration. Antivascular endothelial growth factors now allow better visual outcomes than mere stabilization of vision and other promising treatments are undergoing study at this time. Summary Age-related macular degeneration therapy has undergone a significant revolution in recent years. Understanding the historical perspective of treatment provides a better appreciation of current therapies. Still there is no cure for this disease and more promising treatments are currently under investigation.

Surgical removal of peripapillary choroidal neovascularization associated with age-related macular degeneration.

BACKGROUND AND OBJECTIVE To describe the results of surgical treatment of peripapillary choroidal neovascularization in age-related macular degeneration as an option to both laser photocoagulation and photodynamic therapy. PATIENTS AND METHODS Retrospective review of patients with peripapillary choroidal neovascularization secondary to age-related macular degeneration who were not eligible for or refused laser photocoagulation. Patients without the diagnosis of age-related macular degeneration and those who had extension of their neovascularization subfoveally were excluded from the review. RESULTS Eleven patients total were identified who met the specified inclusion criteria. The male to female ratio was 4:7, with an age range of 63 to 94 years (mean = 78 years). The mean area of involved retina temporal to the optic disc was 5 clock hours, with the distance of the temporal edge of the lesion from the fovea ranging from 100 to 2,000 microm. The mean duration of follow-up was 23 months, with 27% (3 of 11) experiencing recurrent choroidal neovascularization. The preoperative and postoperative visual acuity ranges were both 20/25 to counting fingers. Sixty-four percent (7 of 11) of patients had stable or improved visual acuity postoperatively, with a mean visual acuity change of 1 line visual improvement. CONCLUSION In cases where photodynamic therapy and laser photocoagulation are not indicated, the surgical treatment of peripapillary choroidal neovascularization secondary to age-related macular degeneration may prove beneficial.

A new and improved vitreoretinal erbium:YAG laser scalpel: long-term morphologic characteristics of retinal-choroidal injury.

BACKGROUND AND OBJECTIVE To report a modified erbium:YAG laser scalpel designed to incise tissue more efficiently and safely than other systems reported to date. MATERIALS AND METHODS An erbium:YAG laser delivery system was built to deliver laser energy in bursts of micropulses with a repetition rate of 1,000 Hz. The laser was coupled to handpieces with tip designs equipped with shields, backstops, and beveled, straight, and flexible fibers. In vivo studies in the rabbit eye were performed to determine damage threshold, optimal pulse energy, and burst frequency required to make incisions in the retina and choroid. The safety profile and directional control provided by the handpieces were tested for consistency. Partial- and full-thickness retinal-choroidal incisions were examined clinically and histologically at various time intervals. RESULTS The best incisions were obtained at a fluence of 3.5 J/cm2 or greater, a burst repetition rate of 10 to 40 Hz, and 6 micropulses per burst. Retinal damage occurred when incising laser energy was used 500 microm or closer to the retinal surface. Depth of penetration of laser energy did not depend on burst repetition rate. The use of laser endoprobes equipped with shields and backstops provides absolute protection from stray laser energy in aqueous media. The use of flexible beveled fiber tips provides reliable, accurate directional control. Retinal-choroidal incisions and damage resulted in local retinal-choroidal degeneration and adhesion formation. CONCLUSION The modifications to the erbium:YAG laser scalpel provide a more efficient, versatile, and safe application to vitreoretinal surgery than any system reported to date.

Labor-Induced Hemorrhage of a Retinal Cavernous Hemangioma

The authors present a case of a previously undiagnosed retinal cavernous hemangioma that hemorrhaged during labor. There are previous reports of labor-induced intracranial hemorrhage from central nervous system vascular malformations, but none have demonstrated intraocular hemorrhage during labor. The case emphasizes a need to screen patients with retinal cavernous hemangioma and to warn them of possible vision loss during Valsalva maneuvers such as labor.