Luis Amselem

Ocular Findings in Patients with Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes Syndrome

OBJECTIVE Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare disorder. This study investigated the types of ocular signs and symptoms in patients with POEMS and any systemic factors that may be associated with development of such ocular findings. DESIGN Case series from tertiary referral center. PARTICIPANTS A total of 33 patients with POEMS syndrome underwent at least 1 ophthalmologic examination and were included in the study. METHODS A 10-year retrospective chart review of patients diagnosed with POEMS syndrome was performed. MAIN OUTCOME MEASURES Visual symptoms, visual acuity, presence of optic disc edema (ODE), and levels of systemic factors (including plasma vascular endothelial growth factor [VEGF], plasma interlukin-6 [IL-6], and raised intracranial pressure) and their relationship to ODE. RESULTS Five of the patients (15%) reported diplopia, 15 patients (45%) had blurred vision, and 3 patients (9%) had ocular pain. The most common ocular finding was bilateral ODE in 17 patients (52%). Of the patients with ODE, 5 (29%) were asymptomatic at the first ocular examination. Among patients with ODE, there was a significant difference (P = 0.03) between the mean plasma VEGF level at the time of diagnosis of the ODE compared with when the ODE resolved. There was no difference in plasma IL-6 levels between people with and without ODE. Patients with ODE had a higher mean lumbar puncture opening pressure (276±14 mm H(2)O; normal range, 100-250 mm H(2)0) than patients without ODE, although the difference was not statistically significant (P = 0.08). CONCLUSIONS Optic disc edema is a common finding in patients with POEMS. Because patients can be asymptomatic, eye examinations should be performed in all patients with POEMS. There may be an association between elevated VEGF and intracranial pressure and ODE; further studies are required.

Intravitreal bevacizumab (Avastin) for choroidal metastasis secondary to breast carcinoma: short-term follow-up.

Intravitreal bevacizumab (Avastin) for choroidal metastasis secondary to breast carcinoma: short-term follow-up

Retinal pigment epithelial tear following ranibizumab use.

Retinal pigment epithelium (RPE) tears are a major complication in patients with pigment epithelial detachments (PED) secondary to exudative age-related macular degeneration (ARMD). They also occur following treatment of PEDs with photocoagulation, photodynamic therapy, and intraocular injections of bevacizumab (Avastin, Genentech) and pegabtanib sodium (Macugen, Eyetech Pharmaceutical). In this report, we describe a patient who developed an RPE tear following an intravitreal injection of ranibizumab (Lucentis, Genentech).

Papulopustular eruption after intravitreal bevacizumab (Avastin).

Editor, A 61-year-old White woman came to our institution complaining of blurred vision in her left eye. She was taking no medication and had no relevant medical history. On examination, she had a right best-corrected visual acuity (BCVA) of 20 ⁄ 20 and a left BCVA of 20 ⁄ 80. The spherical equivalent refractive error was )7.0 D in the right eye and )10.0 D in the left eye. Choroidal neovascularization secondary to pathological myopia in the left eye was diagnosed. An uneventful intravitreal injection of bevacizumab (2.5 mg) was performed in the left eye. The patient exhibited a positive response to bevacizumab except for the development of multiple scattered, erythematous papules involving especially the head and trunk, which started 6 days after the intravitreal injection (Fig. 1). A skin-punch biopsy revealed hyperkeratotic follicular infundibulum with a surrounding dermal inflammatory cell infiltrate. Three weeks after the injection, BCVA improved to 20 ⁄50. Two months after the initial presentation, the patient had another sudden reduction in left visual acuity. The left BCVA had decreased to 20 ⁄40 and a second intravitreal injection of bevacizumab (2.5 mg) was performed in the left eye with good results. Five days after the injection, appearance of papulopustular reaction on her forehead was again documented. After 6 months of follow-up, the left visual acuity remains at 20 ⁄ 40. Bevacizumab is a monoclonal antibody to vascular endothelial growth factor (VEGF), a key mediator in tumour angiogenesis. VEGF receptors are overexpressed in various retinal disorders, including age-related macular degeneration (ARMD), diabetic retinopathy and myopic choroidal neovascularization (Sakaguchi et al. 2007). The drug is Food and Drug Administration (FDA)-approved for use in oncology patients in combination with different chemotherapeutic agents and has been used off-label with some success in treating neovascularization in ARMD, diabetic retinopathy and myopic choroidal neovascularization (Sakaguchi et al. 2007). In this case of choroidal neovascularization secondary to pathological myopia, a dose of 2.5 mg bevacizumab was injected intravitreally. Although comparisons of the 2.5and 1.25-mg doses suggest that there is not likely to be a large difference in short-term effect between the two doses, there are no conclusions about their long-term comparative effects (Diabetic Retinopathy Clinical Research Network et al. 2007). Intravenous bevacizumab is typically well tolerated, and its major side-effects include hypertension, proteinuria, bleeding, gastrointestinal perforation and arterial thrombotic events (Gotlib et al. 2006). Although exfoliative dermatitis, with an incidence of 19%, is the most common cutaneous adverse event among patients receiving intravenous bevacizumab, a papulopustular skin rash has also been described (Gotlib et al. 2006). A recent study on the pharmacokinetics of intravitreal bevacizumab (1.25 mg) in the rabbit showed that a maximum serum concentration of 3.3 lg ⁄ml was achieved 8 days after intravitreal injection and the concentration fell below 1 lg ⁄ml 29 days after injection (Bakri et al. 2007). Therefore, systemic complications could potentially occur after intravitreal injection of bevacizumab. Some authors have reported a rate of systemic complications of <4.6% after intravitreal injection of bevacizumab (Arevalo et al. 2007), but none of them have reported any cutaneous reaction. Skin rashes are known to typically develop with epidermal growth factor receptor (EGFR) antagonists, including tyrosine kinase inhibitors and antibodies such as cetuximab (Erbitux ) and erlotinib (Tarceva ). The current theory is that EGFR inhibition results in abnormal epidermal differentiation, which leads to follicular obstruction and subsequent inflammation (Lynch et al. 2007). This toxicity usually occurs in the first 2 weeks of treatment, and affects the face, trunk and extremities. EGFR antagonist-induced skin rashes are characterized by clusters of monomorphic pustular lesions, with a histological examination revealing neutrophilic infiltration of the dermis. The skin rashes are dose-dependent and can improve or resolve spontaneously. The functional similarity of EGFR and VEGF points to the possibility of a correlation between skin Fig. 1. Papulopustular eruption (acneiform rash) after intravitreal bevacizumab (Avastin ): multiple scattered, erythematous papules involving especially the head, 8 days after intravitreal injection of bevacizumab (2.5 mg) in a patient with myopic choroidal neovascularization. Acta Ophthalmologica 2009

Photodynamic Therapy For Symptomatic Subretinal Fluid Related To Choroidal Nevus

Purpose: The purpose of this article is to evaluate the role of photodynamic therapy (PDT) for symptomatic choroidal nevus with subretinal fluid (SRF) extending to the fovea. Methods: Retrospective review of the medical records of all patients who underwent PDT for a symptomatic choroidal nevus with SRF. Results: Seventeen patients were included in the study. The mean initial visual acuity was 20/80 (range, counting fingers to 20/20). The mean initial tumor thickness was 1.23 mm (range, 0.66–1.93 mm). All tumors presented at least 2 risk factors for growing (including orange pigment, symptoms, peripapillary location, SRF, and thickness >2 mm). The mean number of PDT sessions was 1.41 (range, 1–3). The mean final visual acuity improved to 20/60 (range, counting fingers to 20/20). Subretinal fluid was reduced in all eyes (100%) and had completely disappeared in 9 eyes (53%) after PDT. Of 9 cases with complete resolution of the SRF, 2 patients (22%) presented recurrence. The mean final tumor thickness increased to 1.24 mm (range, 0.66–2.01 mm) at a mean follow-up of 22.47 months (range, 6–60 months). Tumor thickness increased in 3 eyes (18%) and remained unchanged in 13 eyes (76%), and 1 lesion (6%) shrank down to a flat chorioretinal scar. Conclusion: Photodynamic therapy is a good treatment option to reduce SRF in symptomatic choroidal nevus with serous macular detachment. Further growth into melanoma was observed in 18% of cases. Thus, PDT may not allow a good local tumor control. Longer follow-up is required to determine its value in these patients.

Changes in fundus autofluorescence of choroidal melanomas following treatment

PurposeWe have previously shown that fundus autofluorescence (FAF) associated with pigmented choroidal lesions can be attributed to mainly lipofuscin (orange pigment) but also to hyperpigmentation, drusen, or fibrous metaplasia. The purpose of this study is to describe the effects of treatment on FAF in choroidal melanomas after plaque radiotherapy alone or in combination with transpupillary thermotherapy (TTT).MethodsRetrospective chart review of eight consecutive patients with choroidal melanoma treated with plaque radiotherapy alone or in combination with TTT who underwent FAF photography before and after treatment. The correlation between FAF patterns and foci of orange pigment, hyperpigmentation, drusen, or fibrous metaplasia was evaluated.ResultsThe median follow-up time was 4 (range 2–9) months. Foci of orange pigment and hyperpigmentation became larger and more numerous after treatment. Fibrous metaplasia was also increased. A complete correlation between increased FAF and orange pigment was found in all eight tumours (100%) before and after treatment. No correlation between hyperpigmentation and increased FAF was found before treatment but a partial correlation was found in all eyes after treatment. Before treatment, correlation between fibrous metaplasia was present in three eyes and increased FAF was partial in two eyes with no correlation in one case. After treatment, this correlation was partial in all presenting eyes (7).ConclusionsFollowing treatment, choroidal melanomas may show increased FAF, mainly due to an increase in the amount of lipofuscin (orange pigment) and hyperpigmentation.

Infrared reflectance in choroidal melanomas and its correlation with fundus autofluorescence

Choroidal melanoma is the most common primary malignant intraocular tumour, with a 50% mortality after 10 years.1 There is considerable evidence that most uveal melanomas arise from pre-existing melanocytic nevi. Orange pigment (lipofuscin) is one of the risk factors for malignancy of a choroidal melanocytic lesion. Since the risk of tumour growth depends on the number of risk factors present,2 it is important to accurately determine the presence or absence of each of these. The greater penetration of infrared light compared with visible wavelengths permits better visualisation of subretinal structures.3 4 We have previously shown that fundus autofluorescence (FAF) improves visualisation of lipofuscin (orange pigment) and subretinal fluid in pigmented choroidal melanomas in comparison with conventional fundus photography.5 6 …

Pegaptanib sodium for acute retinal necrosis- induced macular oedema

35-year-old immunocompromisedwoman with umbilical cordblood transplantation for adult lym-phoma presented with a 2-week his-tory of redness and blurred vision inboth eyes following initial herpes zos-ter encephalitis. Examination revealedvitritis, retinal whitening (Fig. 1), vas-culitis and optic nerve head oedema.Best-corrected visual acuity (BCVA)was 20⁄40 right eye (OD) and 20⁄60left eye (OS). Optical coherencetomography (OCT) showed no cystoidmacular oedema (CMO).Polymerase chain reaction testing ofthe aqueous fluid revealed varicellazoster virus and the patient was diag-nosed with bilateral acute retinalnecrosis (ARN).The retinitis was controlled withoral valacyclovir and intravitrealfoscarnet (2.4 mg) every 3 days,followed 10 days later by pars-planavitrectomy and endolaser in both eyes.BCVA improved to 20⁄25 OD and20⁄20 OS with no signs of ocularinflammation.One month later, the clinical coursewas complicated by severe CMO inthe right eye with a central fovealthickness of 410 lm and a BCVA of20⁄60, with no signs of ocular inflam-mation.After discussion of periocularand⁄or intravitreal use of steroids, thepatient refused to have this treatmentbecause of his family history of glau-coma and the increased potential riskof cataract formation. After a lengthydiscussion of the potential risks andbenefits of off-label intravitreal bev-acizumab or intravitreal pegaptanibsodium use, the patient requestedintravitreal pegaptanib sodium.An intravitreal injection of pegap-tanib sodium (Macugen; Eyetech⁄Pfizer, New York, NY, USA) wasadministered in the right eye withoutcomplication. Two weeks after injec-tion, OCT demonstrated a markedimprovement of the macular oedema,with a central foveal thickness of 197lm and a BCVA of 20⁄25 in theright eye (Fig. 2). Three months aftertreatment, there was no ocularinflammation and the OCT revealedno CMO.Acute retinal necrosis (ARN) syn-drome is a distinct infectious retinitiscaused by members of the herpes virusfamily that can impair vision. Itoccurs mostly in adult patients,especially those severely immunocom-promised, in association with a reacti-vation of a herpes virus infection (Lauet al. 2007).Active vasculitis is characterized byvascular sheathing and perivascularintraretinal haemorrhages. Vesselobstruction affects the central retinalartery more often than the vein and isa contributing factor to severe visionloss (Chang & Young 2007). Retinalischaemia is the major trigger ofvascular endothelial growth factor(VEGF) over-expression; it can leadto chronic inflammation and thedevelopment of retinal neovasculari-zation (Nishijima et al. 2007).Active inflammation secondary toARN progresses despite antiviraltreatment. High-dose systemic cortico-steroid therapy improves intraocularinflammation and improves vitreousopacity (Chang & Young 2007).However, some patients have CMOthat is resistant or non-responsive tosteroids.Bevacizumab is an anti-VEGFmonoclonal antibody that blocksall VEGF isoforms. Intravitrealbevacizumab has been used success-fully for the treatment of uveitic-resistant CMO (Cordero Coma et al.2007) with short-term improvementin BCVA and decreased OCT retinalthickness in a considerable propor-tion of patients. However, VEGF-Ais a survival factor for retinal neu-rons and a critical neuroprotectantduring the adaptative response toischaemic injury (Nishijima et al.2007).Pegaptanib sodium is a selectiveRNA aptamer that inhibits VEGF-165, the VEGF isoform primarilyresponsible for pathological ocularneovascularization and vascular per-meability, while sparing the physiolog-ical isoform VEGF-121. Retrospectivedata suggest that pegaptanib may pro-vide therapeutic benefit for patientswith diabetic macular oedema, prolif-erative diabetic retinopathy and reti-nal vein occlusion (Ng & Adamis2006).

Photodynamic therapy of symptomatic choroidal nevi

Purpose: To evaluate the role of photodynamic therapy (PDT) for patients with symptomatic choroidal nevi involving the fovea or located near the fovea with subretinal fluid extending to the fovea. Materials and Methods: Retrospective review of five patients who underwent PDT for choroidal nevi at two separate centers in Ankara and Barcelona. Results: The mean initial logMAR visual acuity was 0.5 (range: 0 to 1.5). The mean largest tumor base diameter was 3.2 mm (range: 2.1–4.5 mm) and the mean tumor thickness was 1.1 mm (range: 0.7–1.6 mm). The mean number of PDT sessions was 1.6 (range:1–3). The mean final tumor thickness was 1.0 mm (range: 0–1.6 mm) at a mean follow-up of 19 months (range: 12–32 months). The mean final logMAR visual acuity was 0.4 (range: 0–1.5). Subfoveal fluid disappeared or decreased significantly in 4 of 5 eyes (80%) after PDT. Conclusions: PDT led to resolution of subretinal fluid with preservation of visual acuity in many symptomatic choroidal nevi in this study. Careful case selection is important as PDT of indeterminate pigmented tumors may delay the diagnosis and treatment of an early choroidal melanoma and thereby increase the risk for metastasis.

Anti–vascular Endothelial Growth Factor Therapy for Myopic Choroidal Neovascularisation

Pathological myopia represents the most common cause of choroidal neovascularisation in young patients. its natural course has a devastating prognosis. Several treatments have been assessed, but photodynamic therapy is currently the only approved treatment for subfoveal choroidal neovascularisation related to pathological myopia. anti-vascular endothelial growth factor therapy has demonstrated promising results in any form and localisation of choroidal neovascularisation, although there is an absence of data obtained from randomised clinical trials. The aim of this article is to compare different treatment options, combinations and retreatment criteria for the management of choroidal neovascularisation in eyes with high myopia.