Alfonso Giovannini

Photodynamic therapy of circumscribed choroidal hemangioma

PURPOSE To evaluate the safety and effectiveness of photodynamic therapy (PDT) in the treatment of symptomatic circumscribed choroidal hemangiomas (CCH) of the posterior pole. DESIGN Prospective, consecutive, noncomparative case series. PARTICIPANTS Ten eyes of 10 patients (six males and four females; age range, 38-64 years) reporting visual impairment caused by intraocular CCH. Follow-up was 7 to 16 months. METHODS Photodynamic therapy was applied by Zeiss laser (Visulas 6905, Carl Zeiss-Meditech AG, Jeud Germany) emitting a light at 689 nm for photosensitization and by using verteporfin (Visudyne; Novartis Ophthalmics AG, Basel, Switzerland) at a dose of 6 mg/m(2) body surface administered intravenously before treatment. The diameter of the treatment spot was calculated on early frames of pretreatment indocyanine green angiography; the maximum treatment spot diameter was 6000 micro m using a Mainster wide-field lens (Ocular Instruments Inc., Bellevue, WA USA). In the case of peripapillary CCH, the laser spot was applied at a distance of 200 micro m from the optic disc edge. A laser beam was applied to the retina 15 minutes after the start of the infusion. Two different treatment procedures were used according to the height of the lesion. A radiant exposure of 100 J/cm(2) with an exposure time of 186 seconds was applied to lesions larger than 2 mm. For lesions smaller than 2 mm, a radiant exposure of 75 J/cm(2) with an exposure time of 125 seconds was used. MAIN OUTCOME MEASURES Visual outcomes, pretreatment findings, and final findings were evaluated using biomicroscopy, fluorescein angiography (FA), indocyanine green angiography (ICGA), and ultrasound. RESULTS After a follow-up of 7 to 16 months, FA and ICGA verified the nonperfusion of the vascular channels of the tumor in the treated areas. No retinal pigment epithelium (RPE) changes were observed in the patients who had undergone two PDT treatments, whereas minimal alterations were detected in two of the four patients who had undergone three treatment sessions. Angiographic cystoid macular edema and exudative macular detachment had completely regressed in all cases. Minimal intraretinal edema was observed on the FA frames in two cases. Ultrasound examination found no measurable tumor height in six (60%) cases and a marked reduction in the remaining four cases, even after one treatment (post treatment tumor height range, 0.86-1.82 mm). An improvement in visual acuity (one to six lines on the Early Treatment for Diabetic Retinopathy Study chart) was observed in all the cases. In four cases, the visual acuity returned to 20/20, of which three were extrafoveal and one was subfoveal with visual impairment caused by secondary exudative macular detachment without significant RPE alterations. Also in longstanding subfoveal cases, a marked visual acuity improvement was detected resulting from the disappearance of subretinal or intraretinal fluid, even if functional results were limited by pre-existing RPE alterations. In all cases no damage to retinal vessels was observed. CONCLUSIONS Photodynamic therapy is a minimally invasive but effective method of treatment for CCH and may be considered as a treatment of choice, especially in patients with foveal location of the tumor. Because of its safety and repeatability, this technique can be used to treat frequent recurrences of the tumor.

Polypoidal choroidal vasculopathy in Italy.

Purpose To report on the frequency and clinical features of polypoidal choroidal vasculopathy (PCV) in a consecutive series of elderly Italian patients presenting with macular exudation. Methods The authors conducted a retrospective study on a series of 194 consecutive patients 50 years or older with newly diagnosed exudative maculopathy and the presumed diagnosis of age-related macular degeneration (ARMD). Color and/or red-free photographs and fluorescein and indocyanine green angiography were performed in all patients. Results Of the 194 patients, 19 (9.8%) were diagnosed with PCV. The remaining 175 (90.2%) patients had ARMD complicated by choroidal neovascularization. No age or sex differences were observed between the two groups. The disease was unilateral in 103 (58.9%) of 175 ARMD cases compared with 15 (78.9%) of 19 PCV cases (P = 0.09). Nine (47.3%) of 19 patients with PCV had an extramacular choroidal neovascularization, compared with only 5 (2.9%) of 175 patients with ARMD (P < 0.0001). Significant drusen were present in the fellow eyes of 66 (64.1%) of 103 unilateral cases in the ARMD group and in 4 (26.7%) of 15 patients with unilateral disease in the PCV group (P = 0.006). Conclusions Polypoidal choroidal vasculopathy is not an uncommon disease in Italy and should be suspected in patients presenting with extramacular lesions and no large drusen in the fellow eye.

Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 18-Month Results of the Phase 3 GALILEO Study

PURPOSE To evaluate intravitreal aflibercept for treatment of macular edema secondary to central retinal vein occlusion (CRVO). DESIGN Randomized, double-masked, phase 3 study. METHODS A total of 177 patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n = 106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients were monitored every 4 weeks; the former group received intravitreal aflibercept as needed (PRN), and the sham group received sham. From weeks 52 to 76, patients were monitored every 8 weeks, and both groups received intravitreal aflibercept PRN. The primary endpoint (proportion of patients who gained ≥15 letters) was at week 24. This study reports exploratory outcomes at week 76. RESULTS The proportion of patients who gained ≥15 letters in the intravitreal aflibercept and sham groups was 60.2% vs 22.1% at week 24 (patients discontinued before week 24 were considered nonresponders; P < .0001), 60.2% vs 32.4% at week 52 (last observation carried forward, P < .001), and 57.3% vs 29.4% at week 76 (last observation carried forward; P < .001). Mean μm change from baseline central retinal thickness was -448.6 vs -169.3 at week 24 (P < .0001), -423.5 vs -219.3 at week 52 (P < .0001), and -389.4 vs -306.4 at week 76 (P = .1122). Over 76 weeks, the most common ocular serious adverse event in the intravitreal aflibercept group was macular edema (3.8%). CONCLUSIONS The visual and anatomic improvements seen after fixed, monthly dosing at week 24 were largely maintained when treatment intervals were extended. Patients with macular edema following CRVO benefited from early treatment with intravitreal aflibercept.

Choroidal findings in the course of idiopathic serous pigment epithelium detachment detected by indocyanine green videoangiography.

Purpose: To analyze the choroidal alterations associated with idiopathic serous pigment epithelium detachment. Methods: Twenty‐five consecutive patients affected by idiopathic serous pigment epithelium detachment underwent ophthalmoscopy, fluorescein angiography, and indocyanine green videoangiography. Results: On indocyanine green videoangiography an early, complete, and homogeneous filling of the pigment epithelium detachment was always observed. In the late phases, the indocyanine green pattern depended on the size of the detachment. An idiopathic serous pigment epithelium detachment larger than the diameter of one optic disk was still hyperfluorescent in the late phases of indocyanine green videoangiography and was surrounded by a ring of brighter hyperfluorescence. An idiopathic serous pigment epithelium detachment smaller than the diameter of one optic disk usually could be visualized in the late phases as a hypofluorescent area surrounded by a hyperfluorescent ring. In 30 eyes (83.3%), choroidal hyperpermeability was observed. An irregular dilatation of the choroidal veins at the site or within an area the size of one disk diameter from the detachments could be visualized on indocyanine green videoangiography in 12 of 36 affected eyes (33.3%); in three cases an active focus of central serous chorioretinopathy with subretinal leakage developed in the follow‐up period. Conclusion: The observation that pigment epithelium detachments frequently are associated with choroidal leakage and venous dilatation supports the hypothesis that an idiopathic serous pigment epithelium detachment is a variant of central serous chorioretinopathy. Moreover, the choroidal permeability alterations detected by indocyanine green videoangiography would support the theory of Gass that idiopathic serous pigment epithelium detachments could be caused by exudation of fluids from the choroidal vessels.

Long-term control of choroidal neovascularization secondary to angioid streaks treated with intravitreal Bevacizumab (Avastin®)

Aim: To evaluate the efficacy of intravitreal bevacizumab (IB) in the long-term control of subfoveal choroidal neovascularisation (CNV) associated with angioid streaks (AS). Methods: Patients with unilateral active CNV associated with AS were enrolled. Exclusion criteria were previous treatment for CNV and comorbidity. Postoperative visual acuity was defined as a gain or loss of two or more lines of best-corrected visual acuity (BCVA). Post-treatment CNV size was dichotomised into “increased,” if the CNV area had grown by ⩾200 μm2, and “stable/reduced” if it had decreased by ⩾200 μm2 or had not changed by more than 200 μm2. Patients were retreated if no further improvement or worsening was noted. Results: Patients were five males and six females aged 33 to 58 years (mean 46.8 (SD 9.2)), who received a mean number of 3.5 (1.3) IB treatments (min: 2; max: 6). The mean retreatment interval was 3 (1.5) months (min: 1; max: 6). The mean follow-up duration was 23.8 (2.9) months. At 20 months all patients had stable/reduced CNV size and stable/improved BCVA. The mean BCVA rose significantly from 0.28 (0.2) at baseline to 0.56 (0.29) at 20 months (p<0.0001). Conclusion: IB is a promising tool for the long-term control of CNV in AS. Further studies are required to validate these findings.

OCT imaging of choroidal neovascularisation and its role in the determination of patients’ eligibility for surgery

AIM To evaluate the optical coherence tomographic characteristics of choroidal neovascularisation (CNV) in age related macular degeneration (AMD) and in idiopathic and inflammatory CNV. The use of this technique in the selection of patients for surgery is discussed. METHODS Ocular coherence tomography (OCT), fluorescein, and indocyanine green angiography were performed in 23 patients affected by AMD complicated by well defined CNV and in 10 patients affected by inflammatory or idiopathic CNV. The neovascular membrane was surgically removed in five age related CNVs, two inflammatory choroidopathies, and two idiopathic CNVs. RESULTS In inflammatory and idiopathic CNV, the OCT displayed a neovascularisation on the retinal pigment epithelium (RPE). In three cases the CNV was excised with an improvement of visual acuity equal to or greater than two Snellen lines; in a fourth case, the visual acuity after surgery was unchanged. In the cases of AMD the OCT fell into three different patterns: (A) CNV above the RPE (five cases); (B) focal, irregular thickening of the retinal pigment epithelial band (12 cases); (C) CNV above and below the RPE (six cases). The five pattern A CNV patients underwent the surgical excision of the neovascularisation. In four cases the visual acuity improved by two or more Snellen lines; in the fifth case the visual acuity remained unchanged. CONCLUSIONS The authors suggest that the surgical removal of early age related CNV could be performed in those cases where the OCT shows a neovascular membrane on the RPE, as in idiopathic and inflammatory CNVs.

Optical coherence tomography in the assessment of retinal pigment epithelial tear.

Purpose: To study the findings of optical coherence tomography (OCT) in retinal pigment epithelial (RPE) tears. Methods: Sixteen eyes of 16 consecutive patients with age‐related macular degeneration complicated by RPE tear were studied using OCT. Fluorescein angiography also was performed. Thirteen eyes were at the acute stage and three eyes were at the scarring stage, still with a recognizable tear. Results: Optical coherence tomography identified an RPE detachment (PED) with focal interruption of the RPE in all cases. Optical coherence tomography always highlighted a peculiar non‐dome‐shaped profile of the serous PED, as opposed to that of the PED not complicated by an RPE tear. A very intense hyperreflectivity was observed in the OCT scans performed through the retracted RPE. A deep hyperreflectivity under the line corresponding to the RPE was evident in the area of the bare choroid. No choroidal neovascularization could be visualized using OCT, either at the acute or at the scarring stages. Conclusions: Optical coherence tomography, a noncontact, noninvasive imaging technique, may be a useful tool, complementary to fluorescein angiography, in the clinical assessment of RPE tears.

Optical coherence tomography findings in diabetic macular edema before and after vitrectomy.

BACKGROUND AND OBJECTIVE To assess the role of optical coherence tomography (OCT) in the evaluation and follow-up after vitrectomy for diabetic macular edema. MATERIALS AND METHODS The 18 eyes of 12 patients affected by presumed diabetic vitreous-induced macular edema underwent biomicroscopy with a Goldmann contact lens, fluorescein angiography, and OCT. RESULTS OCT revealed two patterns of edema. The first group (15 eyes) was characterized by widespread thickening of the neurosensory retina with an increased nonhomogeneous reflectivity of the inner retinal layers; cystoid-like spaces of absent or reduced reflectivity in the neurosensory retina were also present. In the second group (3 eyes), a cystoid macular edema with a dome-shaped foveal profile because of a markedly increased retinal thickness in the foveal region was observed. The disappearance of the physiologic foveal profile was always seen. Biomicroscopy revealed an increased reflex of the inner limiting membrane in the first group and minimal alterations in the second one. Four patients (7 eyes) underwent vitrectomy with posterior hyaloid removal. In 5 eyes, the patients experienced a visual improvement greater than two Snellen lines. The restoration of the normal foveal profile and the reduction of the retinal thickness on the OCT were evident in all cases one month after surgery. CONCLUSION OCT appears to be a useful tool in the diagnosis and management of diabetic macular edema and in the monitoring of the morphological changes after vitrectomy.

Adalimumab (Humira ™ ): a promising monoclonal anti-tumor necrosis factor alpha in ophthalmology

Tumor necrosis factor alpha (TNF-α) is a key soluble mediator involved in the inflammatory cascade of many disorders including uveitis. Among the anti-TNF-α agents, one of the most used in immune-mediated diseases, such as inflammatory arthropathies, is adalimumab (Humira™, Abbott Pharmaceutical Inc.), a fully humanized antibody. The purpose of this review is to analyze the main pharmacological and clinical aspects of adalimumab and its efficacy both in systemic and ocular inflammatory disorders. Adalimumab was effective in treating several autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. In recent years, adalimumab has been used successfully in refractory cases of intraocular inflammation. Moreover, this biological agent showed good safety and efficacy profiles in ocular use including childhood uveitis. Switching from other anti-TNF-α agents to adalimumab may offer several advantages, such as easier administration, better patient compliance, and lower rate of adverse events. Adalimumab is a promising drug for the therapy of uveitis, although further studies are needed on its application in uveitis.

Indocyanine green angiographic findings in serpiginous choroidopathy.

AIMS--Analysis of the choroidal findings in patients affected by serpiginous choroidopathy (SC). METHODS--Thirteen patients (23 eyes; 11 males and two females; age range 50-68 years; mean age 59.1 years) affected by SC were examined with fluorescein angiography (FA) and indocyanine green angiography (ICGA). The follow up period was 7-33 months. RESULTS--Using ICGA the disease could be divided into the following stages: (1) subclinical or choroidal stage (hypofluorescent lesions without FA evidence); (2) active stage (with ICGA and FA evidence); (3) subhealing stage (slight late hyperfluorescent lesions with ICGA, with no evidence on FA); (4) inactive or healed stage (hypofluorescent areas with ICGA and hyperfluorescent areas with FA). CONCLUSIONS--Although FA showed a clear distinction between active and healed stages, ICGA allowed a greater subdivision of the disease. In particular, ICGA allowed: (1) better staging of SC, revealing choroidal alterations when there was no ophthalmoscopic or FA evidence; (2) better identification of the active lesions which appear to be larger at the choroidal level in comparison with the corresponding retinal lesions; and (3) revealed a persistence of choroidal activity even when the signs of retinal activity had disappeared. Thus, ICGA should be a particularly useful clinical and therapeutic monitoring tool of SC.