Predictive factors of visual and anatomical outcome after intravitreal bevacizumab treatment of neovascular age-related macular degeneration: an optical coherence tomography study.

AIM: To evaluate the baseline visual and optical coherence tomography (OCT) factors on outcomes after intravitreal bevacizumab treatment of subfoveal neovascular age-related macular degeneration (AMD). METHODS: A retrospective analysis of 73 eyes treated with intravitreal bevacizumab for subfoveal neovascular AMD was performed. Change in best corrected Snellen visual acuity (BCVA) and central retinal thickness (CRT) on OCT were the primary outcomes. Automated and manual measurements were made for all OCT characteristics. RESULTS: Seventy-three (100%) and 58 (79.5%) eyes were followed for 3 and 6 months, respectively. The mean BCVA improved from 20/177 to 20/160 (p = 0.03) at 3 months and to 20/143 (p = 0.04) at 6 months. The mean CRT decreased 93 microm (p<0.0001) and 105 microm (p<0.0001) at 3 and 6 months, respectively. Baseline BCVA worse than 20/100 was associated with greater visual improvement (p< or =0.04). Eyes with baseline CRT greater than 400 microm experienced a greater mean CRT reduction (p<0.05). Treatment-naïve patients had a greater mean CRT reduction than those previously treated with any modality (p<0.05) CONCLUSIONS: Baseline BCVA and CRT positively influence mean visual and CRT improvement, respectively, after intravitreal bevacizumab in wet AMD. Any prior treatment predicted less CRT reduction.

VEGF inhibitors for the treatment of neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world for those patients aged 50 years or older. Neovascular AMD, a subtype characterized by the growth of new, pathologic blood vessels, results in most of the cases of severe and rapid vision loss associated with AMD. A critical activator of angiogenesis in neovascular AMD is VEGF. Several therapies have been and are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, VEGF receptor decoy VEGF Trap, small interfering RNA-based therapies bevasiranib and AGN211745, sirolimus, and tyrosine kinase inhibitors including vatalanib, pazopanib, TG100801, TG101095, AG013958 and AL39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still investigational in nature offer the potential for further advances.

Photoreceptor status after antivascular endothelial growth factor therapy in exudative age-related macular degeneration.

AIMS: To evaluate the photoreceptor layer status after antivascular endothelial growth factor (VEGF) therapy in choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD) using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Prospective, consecutive case series. METHODS: Twenty-three eyes of 22 patients with CNV secondary to AMD with foveal thickness less than 250 microm after treatment with anti-VEGF therapy and no obvious leakage on time domain OCT, and eight healthy subjects as controls, were imaged with at least one of four different SD-OCT devices. The inner and outer segment (IS/OS) photoreceptor layers were graded, and correlated with various characteristics including visual acuity. RESULTS: The IS/OS layer was detected in eight eyes (35%) of patients with AMD and all eyes (100%) of the healthy control subjects (p = 0.002). Eyes in patients with AMD with preserved IS/OS had a significantly better BCVA and mean change in BCVA, and were more likely not to have had previous laser treatment compared with eyes with absent IS/OS. CONCLUSIONS: SD-OCT is a useful tool to visualise IS/OS status. IS/OS is often absent in patients who have received treatment with anti-VEGF therapy for CNV due to AMD. The IS/OS status after anti-VEFG therapy correlates with BCVA and mean change in vision.

Verteporfin photodynamic therapy and anti-angiogenic drugs: potential for combination therapy in exudative age-related macular degeneration.

OBJECTIVE: To discuss the rationale for combining anti-angiogenic treatment with verteporfin (Visudyne) photodynamic therapy in the management of choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) and evaluate available evidence for the therapeutic benefits of such approaches. SCOPE: The Medline and EMBASE databases were searched in October 2006 to retrieve relevant articles. Additional articles were obtained from the reference lists of retrieved articles, as well as from recent scientific meetings and company websites. FINDINGS: Treatments for CNV due to AMD can be directed at either the vascular component of CNV (the new vessels that proliferate and leak blood and fluid) or the angiogenic component that leads to the development of the condition. Verteporfin targets the vascular component, whereas anti-angiogenic agents (such as pegaptanib and ranibizumab) target key mediators of the angiogenic cascade. The different mechanisms of action of these approaches offer the potential for additive or synergistic effects with combination therapy. In addition, anti-angiogenic agents might counteract upregulation of angiogenic factors (including VEGF) that occur after verteporfin photodynamic therapy. Results from preclinical and clinical studies of the combination of ranibizumab or pegaptanib with verteporfin warrant continued investigation. CONCLUSIONS: The use of anti-angiogenic agents in combination with verteporfin may have the potential to improve visual outcomes and reduce the number of treatments in eyes with CNV due to AMD, and requires further evaluation in randomized, controlled clinical trials.

Ranibizumab for the treatment of neovascular AMD.

Age-related macular degeneration (AMD) is the leading cause of adult blindness among individuals aged 50 and older in the Western world, with the neovascular form of AMD responsible for the most severe and rapid visual loss. Although monotherapy with currently available treatments can slow the rate of loss of vision in eyes with neovascular AMD, they do not significantly improve vision. Vascular endothelial growth factor-A (VEGF-A) plays a critical role in the pathogenesis of neovascular AMD, and ranibizumab is a promising new treatment that targets all VEGF-A isoforms and their biologically active degradation products. Clinical trials have reported that ranibizumab treatment resulted in greater proportions of patients achieving a < 15 letter loss of visual acuity and improved vision at 12 and 24 months than control groups. The incidence of serious ocular and systemic adverse events was low in all ranibizumab trials to date. Currently, ranibizumab is the only treatment for neovascular AMD to demonstrate significant improvement in vision for many patients and represents a major advance in treating neovascular AMD.

Photodynamic therapy of circumscribed choroidal haemangioma.

AIM: To evaluate efficacy of verteporfin ocular photodynamic therapy (PDT) in treatment of 10 patients with a symptomatic circumscribed choroidal haemangioma. DESIGN: Prospective non-randomised, interventional case series and critical review of previously published studies. METHODS: 10 consecutive patients (seven primary, two failed transpupillary thermotherapy (TTT), and one failed external beam radiotherapy) with symptomatic circumscribed choroidal haemangioma were treated using verteporfin 6 mg/m2 given as an intravenous infusion over 10 minutes. Diode laser (690 nm) with an intensity of 600 mW/cm2 for 83 seconds (50 J/cm2) was applied 5 minutes after completion of infusion. Single or multiple partially overlapping spots were applied based on the tumour basal dimensions. Periodic follow up with ophthalmoscopy, ultrasonography, and angiographic studies was performed. RESULTS: All 10 patients showed evidence of regression with flattening of tumour, resolution of subretinal fluid, and reduction of choroidal vasculature on angiograms. The visual acuity either improved or remained stable in eight (80%) patients. Visual loss due to delayed choroidal atrophy was seen in two patients. CONCLUSIONS: Although verteporfin PDT is an effective treatment for management of symptomatic circumscribed choroidal haemangioma, delayed treatment related effects can lead to visual loss.

The effect of arteriovenous sheathotomy on cystoid macular oedema secondary to branch retinal vein occlusion.

BACKGROUND: Arteriovenous (AV) sheathotomy, a potential treatment for branch retinal vein occlusion (BVO), surgically separates retinal vessels at an AV crossing. Relief of the aetiological obstruction, with resolution of cystoid macular oedema (CMO), may result in improved visual acuity. METHODS: A retrospective review of consecutive cases of AV sheathotomy for BVO was undertaken. Eyes were categorised as having resolution (group 1), reduction (group 2), or persistence (group 3) of CMO. Intergroup comparisons were made with regard to preoperative, intraoperative, and postoperative parameters. Preoperative and postoperative visual acuities were compared within each group. RESULTS: Of the 27 eyes identified, eight (29.6%) had resolution, 14 (51.8%) had reduction, and five (18.6%) had persistence of CMO. Median preoperative visual acuity was similar in all groups (1.0, 1.0, 1.3, respectively; p = 0.29). Overall median follow up was 12.0 months (Q1 = 12.0, Q2 = 22.5). Eyes in group 1 had significantly better median postoperative visual acuity than eyes in groups 2 and 3 (0.6, 1.0, 2.0 respectively; p = 0.01). A significantly higher proportion of eyes in group 1 had visual acuity improvement compared with eyes in the other groups (87.5% v 35.7% and 20.0%; p = 0.03). Median postoperative visual acuity was significantly better than median preoperative visual acuity in group 1 eyes only (p = 0.02). A higher percentage of group 1 eyes had evidence of postoperative retinal perfusion (83.0% v 21.43% and 40.0%; p = 0.16). Postoperative retinal detachment occurred in three eyes (11.1%). CONCLUSION: Complete resolution of CMO after AV sheathotomy occurred in one third of patients, and postoperative vision improved significantly in this group. However, in the majority of cases, despite an improvement in CMO, there was no improvement in vision after AV sheathotomy.

Retinal vasculitis and posterior pole "hypopyons" as early signs of acute bacterial endophthalmitis.

PURPOSE: To report a case of acute postoperative bacterial endophthalmitis presenting with retinal vasculitis and posterior pole "hypopyons." DESIGN: Observational case report. METHODS: Observational case report. RESULTS: In a 73-year-old woman, acute postoperative endophthalmitis presented with retinal vasculitis, diffuse retinal hemorrhages, and several posterior pole "hypopyons" that were collections of yellow-white inflammatory debris. The inflammation was located primarily in the posterior one third of the vitreous, and except for severely impaired visual acuity, the classic signs of acute postoperative endophthalmitis were not present until the next day. An immediate pars plana vitrectomy with intravitreal injection of vancomycin, amikacin, and dexamethasone was performed. Vitreous and aqueous cultures grew coagulase-negative Staphylococcus species. After intravenous and topical therapy for endophthalmitis, the inflammation subsided. Eight weeks after the initial cataract surgery, the best corrected visual acuity of the patient was 20/25. CONCLUSION: Acute postoperative bacterial endophthalmitis may present with atypical clinical signs and inflammation located primarily in the retina and posterior vitreous.

Echography of retinoblastoma: histopathologic correlation and serial evaluation after globe-conserving radiotherapy or chemotherapy.

PURPOSE: To assess the sensitivity of echography in detecting retinoblastoma, compare tumor features observed by echography with histopathology data, and assess the usefulness of echography in serially following retinoblastoma tumors after globe-conserving treatments. METHODS: The medical and echography records of all patients treated for retinoblastoma at the Bascom Palmer Eye Institute between 1991 and 1997 were reviewed. All eyes underwent pretreatment echographic evaluation, and eyes treated with external beam radiotherapy, brachytherapy, or chemotherapy underwent serial follow-up echography. RESULTS: Sixty-nine eyes of 48 patients were identified. Echography demonstrated evidence of retinoblastoma in 69 of 69 (100%) eyes and calcification in 63 (91.3%) eyes. Histopathology was superior to echography in detecting optic nerve invasion, extraocular extension, and presence of calcification. CONCLUSION: Echography is a useful adjunct to indirect ophthalmoscopy in establishing the diagnosis of retinoblastoma. While not as specific as histopathology, echographic evaluation before and after treatment of retinoblastoma permits monitoring of treatment response and may aid in detecting recurrent tumor growth or failure to respond to treatment.

Macular traction detachment and diabetic macular edema associated with posterior hyaloidal traction.

PURPOSE: To review the clinical, photographic, fluorescein angiographic, and optical coherence tomographic findings in patients with the diabetic macular traction and edema (DMTE) associated with posterior hyaloidal traction (PHT). METHODS: We performed a prospective review of nine eyes of nine patients with diabetic macular edema (DME) and PHT on clinical examination. The patients had a comprehensive ophthalmic history and examination, color photographs, fluorescein angiography, and optical coherence tomography (OCT). RESULTS: All patients had diabetic retinopathy and DME. Of the nine eyes, eight patients had previous focal or grid photocoagulation. All nine eyes had a thickened, taut, glistening posterior hyaloid on clinical biomicroscopic examination with no posterior vitreous separation. Fluorescein angiography was performed on seven eyes, and all had early hyperfluorescence with deep, diffuse, late leakage in the macular area consistent with DMTE associated with PHT. Optical coherence tomography scans of the macular region revealed retinal thickening in all eyes with a mean retinal thickness of 556.9 +/- 114.7 microns. In addition, eight of the nine eyes had a shallow macular traction detachment associated with PHT. CONCLUSION: Eyes with DME associated with PHT may have a shallow, subclinical, macular detachment. Optical coherence tomography may be useful in evaluating patients with DME to see if a macular detachment is present.

Corticosteroid therapy for optic disc neovascularization secondary to chronic uveitis.

PURPOSE: To report successful corticosteroid treatment of optic disc neovascularization associated with uveitis. METHODS: Retrospective review of medical records. RESULTS: Nine patients were identified with chronic uveitis and optic disc neovascularization without clinical or angiographic evidence of retinal ischemia. Ages ranged from 14 to 37 years (median age, 27). All patients were treated with either oral and/or subtenon's corticosteroids. Partial regression of the neovascularization was observed in all patients within 2 to 6 weeks (median, 5 weeks) after initiating treatment. Eight of nine patients had complete resolution of disc neovascularization at a median of 3 months (range, 2 to 42 months) after initiation of treatment and a median follow-up of 24 months (range, 7 to 144 months). Recurrence of disc neovascularization occurred in two patients, but it regressed again after further corticosteroid therapy. CONCLUSIONS: Optic disc neovascularization may occur in patients with chronic uveitis in the absence of retinal ischemia. This neovascularization can be successfully treated with corticosteroids.

Neurothekeoma palpebrae: a rare nerve sheath tumor arising in the eyelid.

PURPOSE: To report a case of an eyelid neurothekeoma, a rare peripheral nerve sheath tumor. METHODS: Case report. RESULTS: An excisional biopsy, performed on a lesion removed from the upper eyelid of a 76-year-old woman, revealed the clinical and histopathologic features of a neurothekeoma, a tumor consisting of multiple collections of spindle cells in a myxomatous background. Immunohistochemical characterization showed positivity for NK1/C3, neuron-specific enolase, and alcian blue. CONCLUSION: Neurothekeoma palpebrae should be considered in the differential diagnosis of solitary nodules of the eyelids.

Treatment strategies and visual acuity outcomes in chronic postoperative Propionibacterium acnes endophthalmitis.

PURPOSE: To report the treatment strategies and visual acuity outcomes of chronic postoperative endophthalmitis caused by Propionibacterium acnes. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: All patients presenting 8 or more weeks after cataract surgery with intraocular inflammation caused by culture-proven P. acnes infection and treated at two institutions from 1974 through 1996 were included. METHODS: Patients underwent three different initial treatment strategies. The study did not have a defined treatment protocol, but all patients received intraocular antibiotics. Patients were not randomly assigned to the various treatment strategies. MAIN OUTCOME MEASURES: Final visual acuity and effectiveness of various treatment procedures either as initial or follow-up therapy were assessed. RESULTS: Using the 3 initial strategies, 36 patients were treated: (1) intraocular antibiotic injection alone (IOAB; n = 12); (2) pars plana vitrectomy and IOAB injection (PPV; n = 10); and (3) PPV with subtotal capsulectomy and IOAB injection (PPV-PC; n = 14). The number of patients with recurrent or persistent inflammation after one of the three initial treatment strategies were as follows: (1) IOAB alone, 12 (100%); (2) PPV, 5 (50%); and (3) PPV-PC, 2 (14%). None of the patients that underwent subsequent PPV, total capsular bag removal, IOAB injection, and either intraocular lens (IOL) exchange or removal had persistent or recurrent intraocular inflammation. Overall, final visual acuity was 20/40 or better in 18 patients (50%), and a total of 28 patients (78%) retained 20/400 or better vision. The mean follow-up after the last treatment was 2.9 years. CONCLUSIONS: In this series of chronic P. acnes endophthalmitis, initial treatment with IOAB injection alone or vitrectomy without capsulectomy was associated with high rates of recurrent or persistent intraocular inflammation. Pars plana vitrectomy, partial capsulectomy, and IOAB injection without IOL exchange was usually successful on long-term follow-up. In patients with recurrent intraocular inflammation, pars plana vitrectomy, total capsular bag removal, IOAB injection, and IOL exchange or removal was a uniformly successful strategy. In contrast to other types of postoperative endophthalmitis, IOL exchange can be considered in these patients after total capsular bag removal.

Macular translocation for subfoveal choroidal neovascularization in age-related macular degeneration: a prospective study.

PURPOSE: To conduct a prospective study of macular translocation in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. METHODS: In 10 eyes of 10 patients with subfoveal choroidal neovascularization and best-corrected visual acuity ranging from 20/50 to 20/800 (median, 20/111), the fovea was relocated by means of scleral imbrication, intentional retinal detachment with small posterior retinotomies, and partial fluid-air exchange. In two eyes, the choroidal neovascular membranes were removed at the time of macular translocation; in seven eyes they were photocoagulated in the postoperative period; and in one eye the membrane was removed during reoperation to unfold a macular fold. RESULTS: All 10 eyes were followed up for 6 months. The median postoperative foveal displacement was 1286 microm (range, 114 to 1,919 microm). In three eyes (30%), a foveal fold formed postoperatively requiring reoperation, with one of these eyes requiring a second reoperation for a rhegmatogenous retinal detachment. Best-corrected visual acuity improved in four eyes (median, 10.5 letters) and decreased in six eyes (median, 14.5 letters). The median change in visual acuity was a decrease of 5 letters. The final best-corrected visual acuity was 20/80 in two eyes, 20/126 in one eye, 20/160 in four eyes, 20/200 in one eye, 20/250 in one eye, and 20/640 in one eye. CONCLUSIONS: Our initial experience with limited macular translocation suggests that this surgical technique is unpredictable. However, in patients with subfoveal choroidal neovascularization from age-related macular degeneration, it offers the potential for improving visual function and may be associated with less loss of vision than the disease itself, if allowed to progress. Further refinements in surgical indications and technique are needed to make this procedure safer, more predictable, and more beneficial.

Optic nerve head neovascularization in a patient with inactive cytomegalovirus retinitis and immune recovery.

PURPOSE: To report a case of optic nerve head neovascularization in a patient with acquired immunodeficiency syndrome (AIDS) associated with inactive cytomegalovirus retinitis and immune recovery. METHOD: Case report. RESULTS: We examined a 29-year-old man with AIDS and inactive cytomegalovirus retinitis and found vitritis and prominent optic nerve head neovascularization. The patient had been treated with reverse transcriptase and protease inhibitors, resulting in a notable rise in CD4+ lymphocyte count and an undetectable human immunodeficiency virus (HIV)-RNA viral load. No cause of neovascularization other than intraocular inflammation was detected. CONCLUSION: Immune recovery in a setting of inactive cytomegalovirus retinitis can result in optic nerve head neovascularization, as seen in our patient.