Treatment of CNV secondary to presumed ocular histoplasmosis with intravitreal aflibercept 2.0 mg injection.

OBJECTIVE: To assess the efficacy and safety of intravitreal aflibercept injection in the treatment of CNV secondary to presumed ocular histoplasmosis syndrome (POHS). PURPOSE: To assess safety of intravitreal aflibercept for the treatment of CNV secondary to presumed ocular histoplasmosis syndrome. METHODS: Masked, open-label, prospective study. Five subjects will receive 2.0 mg aflibercept injection every 8 weeks with 3 initial monthly doses over a 12 month period. RESULTS: No adverse systemic or ocular were reported. At month six, the mean visual acuity improved by 7.8 ETDRS letters, mean central subfoveal thickness decreased by 38.8 microns and mean OCT volume decreased by 0.076 mm3 . At month twelve, the mean visual acuity improved by 12.4 ETDRS letters, mean central subfoveal thickness decreased by 34.6 microns and mean OCT volume decreased by 0.576 mm3. CONCLUSION: The use of intravitreal 2.0 mg aflibercept injection for the treatment of CNV secondary to presumed ocular histoplasmosis syndrome yielded no systemic or ocular adverse events and produced improvement in visual acuity and reduction of OCT thickness and volume.

Choroidal neovascularisation as an unusual ophthalmic manifestation of cat-scratch disease in an 8-year-old girl.

To report the first case of choroidal neovascularisation (CNV) that appeared during the primary Bartonella henselae infection in an 8-year-old girl. An 8-year-old girl was referred to our clinic complaining of a central scotoma in the right eye. Fundus examination revealed a bilateral disc oedema and in the right eye neuroretinitis with macular star and CNV, which was confirmed by fluorescein angiography. The optical coherence tomography revealed the presence of macular serous retinal detachment. Laboratory analysis showed rising IgM and IgG titres for B. henselae. Cat-scratch disease was diagnosed, and an 8-week treatment with azithromycin was initiated. In addition, an intravitreal injection of ranibizumab was performed in the right eye to treat the CNV. A month later, we decided to administer a systemic antibiotic again for an additional 5 months, due to the persistence of papillitis. Cat-scratch disease should be considered among the different causes of inflammatory CNV secondary to infectious uveitis. Our case was the first described in the literature in which a CNV appeared during the primary infection and not as a later complication. The combination of systemic antibiotic treatment with intravitreal anti-VEGF therapy was a successful choice because it allowed us to obtain the complete resolution of neuroretinitis, associated with the scarring of the choroidal neovascular membrane, with a final visual acuity of 20/20 in both eyes.

Presumed ocular histoplasmosis.

PURPOSE OF REVIEW: To update the knowledge on the risk factors and treatment options for choroidal neovascular membrane due to ocular histoplasmosis and to provide a treatment algorithm. RECENT FINDINGS: Smoking has been shown to be a strong risk factor in the development of choroidal neovascularization. Alleles that have been identified as a risk factor for the development of choroidal neovascularization in age-related macular degeneration have not shown to be associated with Presumed Ocular Histoplasmosis Syndrome-related choroidal neovascularization. Treatment has largely moved away from submacular surgery and macular photocoagulation to antivascular endothelial growth factor therapy. SUMMARY: This review highlights the devastating vision loss that may occur in ocular histoplasmosis from the development of an atrophic scar at the fovea or following choroidal neovascularization. Many therapies have been tried with varied amounts of success. Antivascular endothelial growth factor therapy appears to be the gold-standard treatment with the possibility of combined photodynamic therapy in refractory cases.

Detection of Chlamydia and complement factors in neovascular membranes of patients with age-related macular degeneration.

PURPOSE: To investigate whether Chlamydia pneumoniae and complement factors were present in surgically removed choroidal neovascular membranes (CNV) of patients with age-related macular degeneration (AMD). METHODS: Paraffin sections of 26 CNV were stained for C. pneumoniae or the complement factors H (CFH) and C5, whereas macrophages were identified by positive CD68 staining. Clinical characteristics have been correlated to the immunohistochemical findings. RESULTS: C. pneumoniae was found in 68% of the investigated membranes, and 88% of these membranes were also positive for CD68. Staining for CFH and C5 gave a positive reaction in 68 and 41% of the membranes, respectively. Patients with C5-positive membranes had significantly larger CNV mean area and were younger than patients with CFH-positive membranes at the operation time point. CONCLUSIONS: Correlations between clinical symptoms and complement factor C5 could be shown. The results strengthen the hypothesis of an involvement of the complement system in AMD.

Changes in ocular flora in eyes exposed to ophthalmic antibiotics.

PURPOSE: To determine changes in ocular flora in individuals repeatedly exposed to topical macrolide or fluoroquinolone antibiotics. DESIGN: Prospective, controlled, longitudinal study with 1-year follow-up. PARTICIPANTS: Forty-eight eyes of 24 patients undergoing serial unilateral intravitreal injection for choroidal neovascularization. METHODS: Patients received 4 consecutive monthly unilateral intravitreal injections and were then treated as needed. Each patient was randomized to 1 of 4 antibiotics (azithromycin 1%, gatifloxacin 0.3%, moxifloxacin 0.5%, ofloxacin 0.3%) and used only their assigned antibiotic for 4 days after each injection. Conjunctival cultures of the treated eye and untreated fellow eye (control) were taken at baseline and before each injection. All bacterial isolates were tested for antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc diffusion technique. MAIN OUTCOME MEASURES: Changes in bacteria composition of the conjunctiva over time. RESULTS: In azithromycin-treated eyes, Staphylococcus epidermidis and Staphylococcus aureus accounted for 54.5% and 18.2% of cultured isolates, respectively, at baseline and 90.9% (P<0.01) and 4.5% (P<0.01), respectively, after azithromycin exposure. In fluoroquinolone-treated eyes, 45.7% and 6.5% of cultured isolates at baseline were S epidermidis and S aureus, respectively, but these percentages increased to 63.4% (P<0.03) and 13% (P = 0.24), respectively, after fluoroquinolone exposure. In contrast, the percentage of gram-negative species decreased from 8.7% at baseline to 1.6% (P<0.05) in fluoroquinolone-treated eyes. The percentage of S epidermidis isolated from azithromycin-treated eyes was significantly greater when compared with fellow control eyes (P<0.01) or fluoroquinolone-treated eyes (P<0.01). CONCLUSIONS: The percentage of S epidermidis isolated from the conjunctival surface significantly increases after repeated exposure to azithromycin and to a lesser degree fluoroquinolone antibiotics at the expense of other commensal flora. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Ranibizumab versus photodynamic therapy for presumed ocular histoplasmosis syndrome.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy of ranibizumab in the treatment of choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome. PATIENTS AND METHODS: Patients enrolled in the ranibizumab group received a monthly intravitreal injection of 0.5 mg of ranibizumab. Patients in the photodynamic therapy (PDT) group received a quarterly dosing of intravenous verteporfin coupled with PDT. RESULTS: Mean change in ETDRS visual acuity at 1 year was 19.6 letters in the ranibizumab group versus 21 letters in the PDT group. All patients in the PDT group required rescue ranibizumab therapy. Four of five patients (80%) in the ranibizumab group and one of two patients (50%) in the PDT group showed a greater than 15 letter gain at 1 year. CONCLUSION: Ranibizumab appears to be a safe and effective treatment option for choroidal neovascularization secondary to the presumed ocular histoplasmosis syndrome.

Peripapillary choroidal neovascularisation in the context of ocular syphilis is sensitive to combination antibiotic and corticosteroid treatment.

Peripapillary choroidal neovascularisation (CNV) in the context of ocular syphilis is exceptional and little is known about its natural history and optimal therapeutic management. We report here a case of right eye peripapillary CNV with subretinal fluid encroaching on the fovea in a patient with mild bilateral ocular inflammation and cystoid macular oedema (CMO) in his contralateral eye. Extensive investigations revealed positive serology for active syphilitic infection. The patient received treatment with intravenous benzylpenicillin according to the algorithm for neurosyphilis complemented with oral corticosteroids as prophylaxis against Jarisch-Herxsheimer reaction for a period of 17 days. On the 15th day, receding of subretinal fluid in his right eye to a small pocket around the optic disc was identified as well as resolution of left eye CMO. We suggest that a course of antibiotic treatment for neurosyphilis with the addition of oral corticosteroids may be an effective therapeutic option for CNV in the context of ocular syphilis and thus more invasive treatment approaches are not warranted.

Intravitreal anti-vascular endothelial growth factor therapy for choroidal neovascularization secondary to ocular histoplasmosis syndrome.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is beneficial in treating choroidal neovascularization from age-related macular degeneration, but few long-term studies have shown its efficacy in choroidal neovascularization from ocular histoplasmosis syndrome. Intravitreal anti-VEGF therapy may be effective in cases of choroidal neovascularization because of ocular histoplasmosis syndrome. METHODS: Retrospective chart review of 54 eyes treated with intravitreal anti-VEGF therapy for choroidal neovascularization in ocular histoplasmosis syndrome with >1 year of follow-up after initiation of anti-VEGF treatment was performed. Previous treatment and demographic information were recorded. Visual acuity was recorded for each injection treatment and at the last follow-up visit. The anti-VEGF agent was recorded for each injection treatment. Visual acuity was recorded at the last follow-up visit. RESULTS: Mean visual acuity improved from 20/53 to 20/26 over an average of 26.8 months. Either bevacizumab or ranibizumab were administered on an average of 4.5 injections per patient per year of follow-up. Vision loss was seen in only three eyes with loss limited to a single line of vision. Patients experienced no serious complications from treatment. CONCLUSION: Long-term intravitreal anti-VEGF therapy with bevacizumab or ranibizumab is beneficial in treatment of choroidal neovascularization in ocular histoplasmosis syndrome.

Smoking as a risk factor for choroidal neovascularization secondary to presumed ocular histoplasmosis syndrome.

PURPOSE: To investigate the relationship of smoking to choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS). DESIGN: Retrospective, case-control study. PARTICIPANTS: A total of 568 patients 18 to 50 years of age, 142 of whom were diagnosed with CNV secondary to POHS in a private retina practice between July 1, 2000, and August 1, 2010. Four hundred twenty-six were controls selected from a private comprehensive ophthalmology practice at the same location. METHODS: A retrospective medical record review was performed for all participants. Age, gender, zip code, CNV diagnosis date, insurance status, and smoking status at CNV diagnosis date were collected first for the POHS patients. For each of these 142 patients, 3 randomly selected comprehensive clinic patients, whose visit date fell within 3 months of the corresponding POHS patient's CNV diagnosis date, served as controls. Age, gender, zip code, visit date, reason for visit, insurance type, and smoking status were recorded. Descriptive statistics were calculated for cases and controls. MAIN OUTCOME MEASURES: Logistic regression analyses were performed for both univariate and multivariate models, with CNV secondary to POHS as the main outcome variable and smoking as the main predictor variable, while adjusting for age, gender, insurance type, median household income, and education level. RESULTS: The mean age of patients with CNV secondary to POHS was 39.0±7.1 years, whereas that of the control patients was 35.7±9.1 years. Of the patients with CNV secondary to POHS, 47.2% were current or former smokers (42.3% current, 4.9% former). Of the control patients, 22.5% were current or former smokers (21.8% current, 0.7% former). Age, insurance type, median income, educational attainment, and smoking status were significant in the univariate models. In the final adjusted logistic regression model, only age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.07; P = 0.001), level of educational attainment by zip code (OR, 0.95; 95% CI, 0.92-0.98; P = 0.001) and smoking status (OR, 2.83; 95% CI, 1.86-4.31; P<0.0001) were significant. CONCLUSIONS: The odds of a smoker having CNV secondary to POHS are almost 3 times that of a nonsmoker. In this study, the odds of having CNV secondary to POHS increased with age and decreased with increasing level of educational attainment.

Analysis of outcomes for intravitreal bevacizumab in the treatment of choroidal neovascularization secondary to ocular histoplasmosis.

PURPOSE: To assess the long-term outcomes of intravitreal bevacizumab (IVB) in the treatment of choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS). DESIGN: Retrospective, comparative case series. PARTICIPANTS: Interventional series of 150 eyes in 140 patients treated for subfoveal or juxtafoveal CNV secondary to POHS from January 2006 to January 2010. INTERVENTION: Intravitreal bevacizumab monotherapy or combination IVB and verteporfin photodynamic therapy (IVB/PDT). MAIN OUTCOME MEASURES: Visual acuity (VA) at 12 and 24 months was analyzed. Secondary outcome measures included the number of injections per year and treatment-free intervals. RESULTS: A total of 117 eyes received IVB monotherapy, and 34 eyes underwent combination IVB/PDT treatment. For all patients, the average pretreatment logarithm of minimum angle of resolution (logMAR) was 0.63 (Snellen equivalent 20/86) with a 12-month logMAR VA of 0.45 (Snellen equivalent 20/56) and a 24-month logMAR VA of 0.44 (Snellen equivalent 20/55). The mean follow-up was 21.1 months with an average of 4.24 IVB injections per year. There was no significant difference in initial VA, VA at 12 months, VA at 24 months, or number of eyes with a 3-line gain between the IVB monotherapy and IVB/PDT groups. Thirty-eight percent (39/104) of eyes gained 3 lines or more, and 81.2% (84/104) of subjects had maintained or improved their starting VA at 1 year. The proportion of subjects maintaining a 3-line gain in VA was relatively preserved at 2 years (29.8%, 17/57) and 3 years (30.3%, 10/32) follow-up. There was no increase in the proportion of subjects losing 3 lines or more over 3 years of follow-up. CONCLUSIONS: There is no significant difference in VA outcomes between IVB monotherapy versus IVB/PDT combination therapy. The use of IVB alone or in combination with PDT results in significant visual stabilization in the majority of patients with CNV secondary to POHS.

Choroidal neovascularization enhanced by Chlamydia pneumoniae via Toll-like receptor 2 in the retinal pigment epithelium.

PURPOSE: Choroidal neovascularization (CNV) is directly related to visual loss in persons with age-related macular degeneration (AMD) and other macular disorders. Chlamydia pneumoniae, a prokaryotic pathogen that causes chronic inflammation, is recognized as a risk factor for cardiovascular diseases. In this study, the authors investigated the association between C. pneumoniae infection and AMD using a laser-induced CNV model in mice. METHODS: C57BL/6 mice, myeloid differentiation factor (MyD) 88 knockout (KO) mice, Toll-like receptor (TLR) 2 KO mice, and TLR4 KO mice were used. Experimental CNV was induced by rupturing the Bruch's membrane by laser photocoagulation (PC). Seven days after PC, the eyes were enucleated and the areas of CNV were measured in choroidal flat mounts. Cytokine gene expression by quantitative real-time PCR in the primary cultured retinal pigment epithelium (RPE) cells was also examined. RESULTS: Vitreous injection of the C. pneumoniae antigen increased the size of CNV. Although lipopolysaccharide stimulation can induce multiple cytokines, cultured mouse RPE cells from C57BL/6 mice expressed IL-6 and VEGF, but not TNF-alpha mRNA, in response to C. pneumoniae antigen. RPE cells from either MyD88 KO mice or TLR2 KO mice did not respond to the C. pneumoniae antigen. TLR2 KO mice did not augment the size increase of experimental CNV by C. pneumoniae antigen in vivo. CONCLUSIONS: C. pneumoniae can trigger inflammatory responses in the eye and promote experimental CNV in a TLR2-dependent manner. These data provide experimental evidence to imply persistent C. pneumoniae infection is a risk factor for AMD.

Inflammatory choroidal neovascular membrane in presumed ocular Lyme borreliosis.

INTRODUCTION: Lyme disease is a multisystemic disease with protean ocular manifestations. We describe the occurrence of inflammatory choroidal neovascular membrane (CNVM) in two patients suffering from presumed Lyme disease. METHODS: Descriptive review of the clinical records of two patients. RESULTS: Patient 1: 16-year-old healthy male presenting with a visual acuity of counting fingers [oculus dexter (OD)] and 6/6 [oculus sinister (OS)] 3 months after a tick bite. He had papillitis and an exudative subretinal macular lesion OD. Treatment was started with intravenous (IV) ceftriaxone; a week later, IV methylprednisolone was administered with a tapering dose of oral steroids thereafter. Three months later, VA had improved to 3/60 OD. Patient 2: 38-year-old healthy female presenting with reduced left-eye vision (6/24) 6 weeks after a tick bite. She also suffered from erythema migrans and arthralgias. She had left-eye papillitis, macular haemorrhages and vascular sheathing. Treatment was started with IV ceftriaxone. One month later, there was profound loss of vision with development of CNVM. Treatment was declined by the patient and eventually retinal fibrosis developed. CONCLUSION: Inflammatory CNVM has not been described previously in the setting of ocular Lyme borreliosis. We herein describe the occurrence of inflammatory CNVM in two patients whose diagnosis with Lyme disease was clinically based--both were sero-negative. Visual outcome in the two patients was profoundly impaired because of the ensuing macular scar.

Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the United States, and increasing evidence suggests that it is an inflammatory disease. The prokaryotic obligate intracellular pathogen Chlamydia pneumoniae is emerging as a novel risk factor in cardiovascular disease, and recent sero-epidemiological data suggest that C. pneumoniae infection is also associated with AMD. In this study, we examined choroidal neovascular membrane (CNV) tissue from patients with neovascular AMD for the presence of C. pneumoniae and determined whether the pathogen can dysregulate the function of key cell types in ways that can cause neovascular AMD. Nine CNV removed from patients with neovascular AMD were examined for the presence of C. pneumoniae by immunohistochemistry (IHC) and polymerase chain reaction (PCR); in addition, we performed PCR on nine non-AMD eyes, and IHC on five non-AMD CNV, seven non-AMD eyes, and one internal limiting membrane specimen. Finally, human monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were exposed to C. pneumoniae and assayed in vitro for the production of pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C. pneumoniae was detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced VEGF production by human macrophages, and increased production of IL-8 and MCP-1 by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for C. pneumoniae. These data indicate that a pathogen capable of inducing chronic inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and suggest that infection may contribute to the pathogenesis of AMD.

[Presumed ocular histoplasmosis syndrome]. / Sindromul histoplasmozei oculare prezumate.

Presumed ocular histoplasmosis syndrome is a macular hemorrhagic choroiditis of the young adult. The etiology of this syndrome is uncertain, but can be correlated with some positive reactions to histoplasmosis. The study was carried out on 12 patients, each of them was investigated by functional and objective ocular examinations, laboratory tests, fluorescein angiography and ultrasound examinations. The clinical signs of this syndrome of presumed ocular histoplasmosis were: macular focal lesions, subretinian hemorrhages, detachment of the retinal neurosensorial layer, presence of disseminated choroiditis scars and subretinian neovascularization. The correct evaluation of the choriocapillary perfusion is helpful to institute a proper therapy.

Intravitreal triamcinolone for choroidal neovascularization in ocular histoplasmosis syndrome.

PURPOSE: To report the effects of intravitreal triamcinolone acetonide injections for subfoveal and juxtafoveal choroidal neovascularization (CNV) in ocular histoplasmosis syndrome. METHODS: In a retrospective analysis, the proportion of eyes that gained >or=5 or lost >or=5 and >or=15 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters, best-corrected visual acuity using ETDRS letter score (VA), greatest linear dimension (GLD), and treatment side effects were assessed. RESULTS: Ten patients (five subfoveal, five juxtafoveal CNV; median follow-up: 17 months; range, 6-41 months) were evaluated. Thirty percent gained >or=5 letters, 20% lost 5 to 14 letters, and 50% maintained stable VA. Overall, mean VA and GLD remained stable. Side effects were transient intraocular pressure elevation and mild cataract development. CONCLUSIONS: Intravitreal triamcinolone acetonide for CNV resulting from OHS was found to be relatively safe and showed good visual outcome for both subfoveal and juxtafoveal CNV. Further studies are warranted to evaluate this treatment.

Open retinotomy after submacular surgery.

PURPOSE: To report persistent open retinotomy after submacular surgery in patients with presumed ocular histoplasmosis. METHODS: Retrospective review. Five eyes of 5 patients with submacular choroidal neovascularization associated with presumed ocular histoplasmosis had pars plana vitrectomy, detachment of the posterior hyaloid, and surgical removal of the neovascular complex using the small retinotomy technique. All eyes were followed postoperatively for a mean of 47 months (range, 36 to 73 months). RESULTS: In all 5 patients, the open retinotomy persisted after submacular surgery. No complications were associated with the presence of an open retinotomy. CONCLUSION: Persistence of the retinotomy site may occur after submacular surgery. With follow-up of at least 36 months, no significant complication is associated with an open retinotomy site.