Lawrence P. Chong

Bevacizumab and ranibizumab tachyphylaxis in the treatment of choroidal neovascularisation

Aims To evaluate the effect of switching to bevacizumab or ranibizumab after developing tachyphylaxis during anti-vascular endothelial growth factor (VEGF) therapy for choroidal neovascularisation (CNV). Methods The authors reviewed the records of all patients who received both ranibizumab and bevacizumab for treatment of CNV to identify those who developed tachyphylaxis, defined as optical coherence tomography evidence of initial decreased exudation followed by lack of further reduction or an increase in exudation. Signs of exudation included subreitnal fluid (SRF), pigment epithelial detachment (PED) and/or cystoid macular oedema (CMO). Results 26 eyes were included. 10 were initially treated with bevacizumab and then changed to ranibizumab for persistent SRF, PED and/or CMO. Of these, seven had occult CNV and three had predominantly classic CNV. One eye in the occult CNV group did not respond after being switched to ranibizumab. Six eyes had a positive therapeutic response, after one injection in four eyes, and after two or three injections in one eye each. In the classic group, two responded to ranibizumab and one did not. Sixteen eyes were initially treated with ranibizumab before changing to bevacizumab. Of these, 15 had occult CNV and 1 was predominantly classic. Three of the 16 eyes failed to respond to bevacizumab; 6 improved after one injection and 5 after two injections. Conclusions Patients with CNV who develop tachyphylaxis to ranibizumab or bevacizumab may respond to another anti-VEGF drug. The majority of cases (81%) in this series demonstrated at least some response after switching therapies.

Subretinal neovascular membranes in Vogt-Koyanagi-Harada syndrome

Subretinal neovascular membranes cause late visual loss and are important determinants of final visual acuity in patients with Vogt-Koyanagi-Harada syndrome. The purpose of this study was to determine the prevalence and risk factors associated with the development of subretinal neovascular membranes in Vogt-Koyanagi-Harada syndrome. We reviewed the charts of 58 patients (116 eyes) with Vogt-Koyanagi-Harada syndrome. We separated patients into two groups, one with and one without subretinal membranes. Demographic characteristics, namely age, gender, and race, initial and final visual acuities, duration and method of treatment, anterior chamber and vitreous cell, presence of fundus pigmentary disturbances, and phase of inflammation, were evaluated for each group. Overall, ten eyes (9%) of seven patients developed the subretinal neovascular membranes. Demographic characteristics among the two groups of patients were not markedly different (P > .10). Visual outcome of patients with subretinal membranes was significantly poorer than was that of patients without these membranes (P < .001). Eyes with subretinal membranes had a significantly greater degree of anterior chamber and vitreous inflammation (P < .02), greater incidence of fundus pigmentary disturbances (P < .02), and a greater frequency of chronic recurrent phase of inflammation, marked by recurrence of predominantly anterior chamber, and occasionally posterior segment, inflammation (P < .02). The membranes were located in the peripapillary (four eyes), subfoveal (three eyes), and macular extrafoveal (three eyes) regions.

Pneumocystis Carinii Choroiditis After Long-Term Aerosolized Pentamidine Therapy

Pneumocystis carinii pneumonia is a major cause of morbidity and mortality in patients with the acquired immunodeficiency syndrome. When P. carinii is disseminated, the choroid may be involved and the infection is often fatal. We examined, treated, and followed up two patients who developed choroidal lesions typical of P. carinii while taking aerosolized pentamidine for prophylaxis. The choroidal lesions gradually resolved after three weeks of therapy with intravenous trimethoprim and sulfamethoxazole in one patient, and after three weeks of therapy with parenteral pentamidine in the other patient. The patients did not have clinical or laboratory evidence of P. carinii infection other than in the eye. It thus appears that early ophthalmologic examination may detect disease before it is threatening to sight and allow systemic therapy to be instituted before widely disseminated infection results in a fatal outcome.

Vitreoretinal Traction Created by Conventional Cutters during Vitrectomy

PURPOSE To quantify the vitreous traction created by pneumatic (20-, 23-, and 25-gauge) and electric cutters (20- and 25-gauge) during vitrectomy. DESIGN Experimental study. PARTICIPANTS This is a preclinical study, and no patients were involved. METHODS Five separate cutters for each drive mechanism and gauge (20-, 23-, and 25-gauge pneumatic and 20- and 25-gauge electric) were used for each cut speed at predetermined aspiration rates. The retinal layers of fresh porcine eyes were transfixed with a 0.15-mm steel wire and fixed to the load cell of a strain gauge. The cutter to be assessed was introduced into the eye by a micromanipulator at a 45-degree angle adjacent to the retina. The traction force was determined and evaluated at a distance of 3 and 5 mm from the retina with different vacuum and cut rates. MAIN OUTCOME MEASURES Vacuum, cut speed, force (dynes), distance (millimeters), vitreoretinal traction, and gauge. RESULTS The 20-, 23-, and 25-gauge pneumatic cutters have a range of traction from 2.06 to 37.22 dynes, 3.85 to 15.38 dynes, 5.13 to 27.91 dynes, respectively. The 20- and 25-gauge electric cutters have a range of traction from 3.60 to 41.78 dynes and 5.28 to 27.91 dynes, respectively. All results are related to distance, cut, and aspiration rate. With an increase of 100 mmHg of vacuum/aspiration, the traction increased from 7.89 to 3.14 dynes (e.g., 4.96 for 20-gauge pneumatic). The traction decreased as the cut rate was increased, from 5.71 to 2.51 dynes (e.g., 3.41 for 20-gauge pneumatic). CONCLUSIONS The results indicate that retinal traction increased with increasing aspiration vacuum and proximity to the retina; conversely, retinal traction decreased with increasing cut rate. The present study demonstrates that the effects of aspiration, distance from the retina, and cut rate are crucial factors in the amount of retinal traction created by vitreous cutters. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Combination Therapy for Neovascular Age-related Macular Degeneration Refractory to Anti-Vascular Endothelial Growth Factor Agents

OBJECTIVE To examine the outcomes of combination anti-vascular endothelial growth factor (VEGF) and photodynamic therapy (PDT) for the treatment of neovascular age-related macular degeneration (AMD) refractory to anti-VEGF monotherapy. DESIGN Retrospective, interventional case series. PARTICIPANTS Twenty-six eyes of 26 patients treated with anti-VEGF monotherapy for neovascular AMD with persistent subretinal or intraretinal fluid after at least 3 anti-VEGF injections in the 7 months before combination treatment. INTERVENTION Combination anti-VEGF treatment and PDT. MAIN OUTCOME MEASURES Visual acuity at 1 or 2, 3, and 6 months and central retinal thickness at 1 or 2, 3, and 6 months. Secondary outcome measures were change in number of fluid-free visits and interval between treatments in the 7 months before and 6 months after combination therapy. RESULTS Statistically significant improvements in logarithm of the minimum angle of resolution visual acuities were present at 1 month (P = 0.01) and 3 months (P = 0.01). Significant decreases in central subfield retinal thickness on optic coherence tomography (OCT) were seen at 1 month (P = 4×10(-5)), 3 months (P = 3×10(-4)), and 6 months (P = 4×10(-5)) as compared with precombination treatment OCT scans. The percentage of patient visits with no subretinal fluid increased from 0.5% to 41% after the initiation of combination therapy (P = 1×10(-5)). The interval between treatments increased from once every 1.6 months in the 7 months before combination treatment to once every 2.7 months in the 6 months after combination treatment (P = 0.002). No ocular complications attributable to PDT were seen. CONCLUSIONS Rescue therapy with the combination of anti-VEGF and PDT in eyes that have failed anti-VEGF monotherapy resulted in a mean improvement in vision, a decreased central subfield retinal thickness, and an increase in fluid-free intervals. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Rifabutin-associated hypopyon uveitis in human immunodeficiency virus–negative immunocompetent individuals

OBJECTIVE To report the occurrence of rifabutin-associated hypopyon uveitis in human immunodeficiency virus (HIV)-negative immunocompetent individuals. DESIGN Retrospective case series. PARTICIPANTS Three HIV-negative subjects on rifabutin and clarithromycin for Mycobacterium avium complex infections with hypopyon uveitis are described. One subject was iatrogenically immunosuppressed because of a prior lung transplant. Two subjects had no known immunosuppressive conditions. INTERVENTION Topical and regional steroid therapy. Discontinuation of rifabutin was required in two subjects. MAIN OUTCOME MEASURES Visual acuity, resolution of hypopyon, anterior uveitis, and vitreitis. RESULTS All subjects had resolution of hypopyon after therapy, two within 24 hours of beginning topical steroids. Vitreitis resolved with the discontinuation of rifabutin in two subjects. Chronic low-grade anterior uveitis and vitreitis were observed in the remaining subject, whose rifabutin dose was lowered but not discontinued because of active Mycobacterium avium complex osteomyelitis. CONCLUSIONS Rifabutin-associated uveitis is well described in HIV-positive individuals, but it has been reported only once in an HIV-negative individual. We report two cases of hypopyon uveitis in immunocompetent individuals and one case in an immunosuppressed HIV-negative individual. All three subjects were receiving concurrent rifabutin and clarithromycin. Awareness that this entity can occur in HIV negative and nonimmunosuppressed individuals and that it can mimic infectious endophthalmitis may spare the subject from an invasive workup of systemic infection.

Migration of intraocular silicone oil into the subconjunctival space and orbit through an ahmed glaucoma valve

PURPOSE To report a patient with intraocular silicone oil migration into the subconjunctival space and orbit through an Ahmed glaucoma valve implant. METHODS Observational case report. A 29-year-old female with diabetes mellitus and proliferative diabetic retinopathy underwent three left eye pars plana vitrectomies and ultimately intraocular silicone oil placement for tractional retinal detachment. Subsequently, she developed neovascular glaucoma and underwent an inferotemporal Ahmed glaucoma tube implant, left eye. RESULTS Intraocular silicone oil migrated through the Ahmed glaucoma valve into the subconjunctival space and orbit. Left eye evisceration with silicone oil removal was performed for a blind painful left eye and improvement of appearance. CONCLUSION Silicone oil migration through an Ahmed valve may be observed after retinal detachment repair with intraocular silicone oil. An Ahmed valve may be contraindicated in eyes of patients with intraocular silicone oil.

Clinicopathologic Study of Retinal and Choroidal Biopsies in Intraocular Inflammation

PURPOSE We reviewed the clinical and histopathologic features of 33 intraocular tissue biopsy specimens from 32 patients and assessed the value of retinal and chorioretinal biopsies performed in patients with intraocular inflammation. METHODS Twenty-four endoretinal biopsies and nine chorioretinal or choroidal biopsies were performed. On the basis of clinical indications, the specimens were processed for light microscopy, electron microscopy, immunohistochemical staining, in situ DNA hybridization, and polymerase chain reaction. RESULTS Of the 24 endoretinal biopsy specimens, 19 were from patients with clinical signs suggestive of viral retinitis. Overall, the diagnosis of viral retinitis was suggested by electron microscopy, immunohistochemical staining, in situ DNA hybridization, or polymerase chain reaction in 53% (ten of 19) biopsies. The preoperative diagnosis was confirmed in seven of ten biopsies in cases of suspected cytomegalovirus retinitis, in one of seven biopsies in cases of suspected acute retinal necrosis, and in two of two biopsies in cases of progressive outer retinal necrosis. The remaining five endoretinal biopsies disclosed Candida in one specimen, subretinal fibrosis in one, and chronic inflammation in three. Histologic examination of the nine chorioretinal or choroidal biopsies disclosed lymphoma in two specimens, a subretinal neovascular membrane in one, uveal melanocytic proliferation in one, toxoplasmic retinochoroiditis in one, viral retinitis in one, and long-standing inflammation in three. CONCLUSION In select cases of intraocular inflammation, intraocular tissue biopsies may provide clinically useful information.

Late-Onset Bacterial Endophthalmitis Following Glaucoma Drainage Implantation

Abstract. A clinicopathologic report of late-onset bacterial endophthalmitis 4 years after implantation of a Baerveldt drainage implant is described. An 80-yearold woman with glaucoma presented 8 years after tube shunt implantation with clinical endophthalmitis. During surgical removal of the implant, a small conjunctival buttonhole caused by the suture securing the plate to the sclera was noted to be the only entry site. Vitreous and anterior chamber taps were performed with intravitreal antibiotics. Cultures revealed Streptococcus pneumoniae infection. The pathologic analysis showed epithelialization of the conjunctival buttonhole and diffuse ocular inflammation, mucopurulent material, and fibrovascular membranes. Due to severe pain, the eye was enucleated after 1 week. [Ophthalmic Surg Lasers Imaging 2003;34:128-130.].

Cytomegalovirus papillitis in patients with acquired immune deficiency syndrome. Visual prognosis of patients treated with ganciclovir and/or foscarnet.

BACKGROUND Of those patients with acquired immune deficiency syndrome in whom cytomegaloviral retinitis develops, cytomegaloviral papillitis reportedly develops in up to 4% as well. Although occasionally patients have a good visual outcome, the majority have a poor visual prognosis, with a visual acuity of 20/200 or worse, even with treatment. METHODS To evaluate the effects of prolonged induction with foscarnet or ganciclovir on the visual prognosis of cytomegalovirus (CMV) papillitis, the records of 22 patients seen between 1990 and 1995 at the Los Angeles County-University of Southern California Eye Clinic were reviewed. Papillitis was defined as greater than 270 degrees of disc edema/blurring of the disc margins as seen on direct examination and on color fundus photographs. RESULTS Eighteen patients with a mean initial visual acuity of 20/69 (range, 20/ 15-20/400) were treated with induction doses of intravenous ganciclovir (range, 5-7.5 mg/kg twice daily) or foscarnet (range, 60-90 mg/kg twice or 3 times daily) for a mean of 3.3 weeks. The mean follow-up period was 4.8 months (range, 1-13 months). These patients maintained a mean final visual acuity of 20/68 (range, 20/ 25-20/400) with greater than 90% resolution of the papillitis. The remaining four patients had poor outcomes (visual acuity < 20/400) because of progressive CMV papillitis or retinitis. The median survival time was 4.5 months from the diagnosis of papillitis, but 7 months from the onset of CMV ocular infection. CONCLUSION Patients with CMV papillitis have good visual prognosis when managed with high and prolonged doses of intravenous foscarnet and/or ganciclovir.