Ultra-wide-field fundus photography compared to ophthalmoscopy in diagnosing and classifying major retinal diseases.

To analyze the performance of ultra-wide-field (UWF) fundus photography compared with ophthalmoscopy in identifying and classifying retinal diseases. Patients examined for presumed major retinal disorders were consecutively enrolled. Each patient underwent indirect ophthalmoscopic evaluation, with scleral depression and/or fundus biomicroscopy, when clinically indicated, and mydriatic UWF fundus imaging by means of CLARUS 500™ fundus camera. Each eye was classified by a clinical grader and two image graders in the following groups: normal retina, diabetic retinopathy, vascular abnormalities, macular degenerations and dystrophies, retinal and choroidal tumors, peripheral degenerative lesions and retinal detachment and myopic alterations. 7024 eyes of new patients were included. The inter-grader agreement for images classification was perfect (kappa = 0.998, 95% Confidence Interval (95%CI) = 0.997-0.999), as the two methods concordance for retinal diseases diagnosis (kappa = 0.997, 95%CI = 0.996-0.999) without statistically significant difference. UWF fundus imaging might be an alternative to ophthalmoscopy, since it allows to accurately classify major retinal diseases, widening the range of disorders possibly diagnosed with teleophthalmology. Although the clinician should be aware of the possibility that a minority of the most peripheral lesions may be not entirely visualized, it might be considered a first line diagnostic modality, in the context of a full ophthalmological examination.

Microperimetry in age: related macular degeneration.

Age-related macular degeneration (AMD) is one of the major causes of visual loss and legal blindness in people over 55. Visual function tests are the cornerstone of visual function investigation and any therapeutic approach to AMD implies, as primary endpoint, the maintenance or improvement of visual function. The progression of visual impairment and the quantification of final residual visual function are currently determined by means of visual acuity quantification. The quantification of high-contrast visual acuity though has many drawbacks and cannot be considered a complete functional examination. Microperimetry is a non-invasive method used to analyse fixation and central visual field defects in a topographic related manner. The introduction of mesopic and more recently scotopic microperimetry, in research and clinical practice of macular disorders, now allows us to better investigate macular function as it strictly relates to macular morphology. We therefore can monitor the functional natural history and quantify the beneficial or detrimental effects of different therapies. The application of microperimetry in clinical studies has provided interesting diagnostic and prognostic information on functional macular changes in AMD patients. The present review brings new updates on the correlation between macular changes, mainly described with optical coherence tomography, and microperimetry changes in patients with AMD.

Descriptive epidemiology of malignant mucosal and uveal melanomas and adnexal skin carcinomas in Europe.

This work provides descriptive epidemiological data of malignant mucosal and uveal melanomas and adnexal skin carcinomas in Europe as defined as in the RARECARE project. We analysed 8669 incident cases registered in the period 1995-2002 by 76 population-based cancer registries (CRs), and followed up for vital status to 31st December 2003. Age-standardised incidence to the European standard population was obtained restricting the analysis to 8416 cancer cases collected by 64 not specialised CRs or with information available only for some anatomical sites. Period survival rates at 2000-2002 were estimated on 45 CRs data. Twenty-two CRs which covered the period 1988-2002 were analysed to obtain the 15-year prevalence (1st January 2003 as reference date). Complete prevalence was calculated by using the completeness index method which estimates surviving cases diagnosed prior to 1988 ('unobserved' prevalence). The expected number of new cases per year and of prevalent cases in Europe was then obtained multiplying the crude incidence and complete prevalence rates to the European population at 2008. We estimated 5204 new cases per year (10.5 per million) to occur in Europe, of which 48.7% were melanomas of uvea, 24.8% melanomas of mucosa and 26.5% adnexal carcinomas of the skin. Five-year relative survival was 40.6% and 68.9% for mucosal and uveal melanomas, respectively. Adnexal skin carcinomas showed a good prognosis with a survival of 87.7% 5 years after diagnosis. Northern Europe, United Kingdom (UK) and Ireland showed the highest 5-year survival rate for uveal melanomas (72.6% and 73.4%), while Southern Europe showed the lowest rate (63.7%). More than 50,000 persons with a past diagnosis of one of these rare cancers were estimated to be alive at 2008 in Europe, most of them (58.8%, n=29,676) being patients with uveal melanoma. Due to the good prognosis and high incidence of uveal melanomas, these malignancies are highly represented among the long-term survivors of the studied rare cancer types. Therefore, maximising quality of life is particularly important in treatment of uveal melanoma. As regards mucosal melanomas, the centralisation of treatment to a select number of specialist centres as well as the establishment of expert pathology panels should be promoted. The geographical differences in incidence and survival should be further investigated analysing the centre of treatment, the stage at diagnosis and the treatment.

In vivo confocal microscopy of ocular surface squamous neoplasia.

PURPOSE: To analyse in vivo structural and cellular features of ocular surface squamous neoplasia using clinical confocal microscopy. METHODS: Ten consecutive cases of untreated ocular surface squamous neoplasia were in vivo investigated using clinical confocal microscopy (ConfoScan4, Nidek Co. Ltd, Gamagori, Japan) with a × 40 surface non-contact objective lens. Confocal microscopy images were compared with cytologic samples obtained by scraping technique. RESULTS: Confocal microscopy examination revealed large areas of superficial cells debris and/or keratin debris accompanied by syncytial-like groupings, loss of the normal structure of the conjunctival epithelium and or of the corneal basal epithelium layer, papillomatous organization, large fibrovascular structures, and fine vessels perpendicular to the tumour surface. Sub-epithelial (pre-Bowman) space involvement was documented in four cases (50%). Irregular healthy tissue infiltration at the lateral edge of the lesion was documented in two cases (20%) whereas abrupt demarcation between neoplastic cells and normal epithelium was documented in eight cases (80%). In vivo cyto-morphologic study using clinical confocal microscopy showed cellular anisocytosis, pleocytosis, and anisonucleosis, enlarged nuclei with high nuclear to cytoplasmic ratio, high reflective cytoplasm and indistinct cytoplasmic borders in all cases (100%) . CONCLUSION: CCM appears to be a promising and non-invasive method for in vivo structural and cellular analysis of OSSN.

Long-term follow-up with optical coherence tomography and microperimetry in eyes with metamorphopsia after macula-off retinal detachment repair.

PURPOSE: to report the long-term sequential morphological and functional results in eyes with metamorphopsia after retinal detachment (RD) repair. PATIENTS AND METHODS: in six eyes of six patients aged 58.7 ± 11.0 years with metamorphopsia after successful buckling surgery for macula-off RD, best-corrected visual acuity (BCVA), fundus biomicroscopy, Amsler grid test, time-domain optical coherence tomography (TD-OCT) and central 12° microperimetry (MP-1) were performed at months 1, 3, 6, 12, and 18. At 5 to 6 years after surgery all patients underwent also spectral domain (SD)-OCT. RESULTS: three eyes slowly recovered pre-RD BCVA. In the remaining three eyes-with good final BCVA-the interrupted junction line between photoreceptor cell inner and outer segments (IS/OS) was progressively less evident after RD surgery; and the external limiting membrane was preserved on SD-OCT examination. In all eyes post-operative metamorphopsia faded with time, but fully disappeared in 6 years only in two eyes without photoreceptor abnormalities. One of the two eyes with subretinal fluid up to 6 months and IS/OS disruption had central dense scotoma with relatively unstable fixation on MP-1 and persistent metamorphopsia. Macular sensitivity (MS) increased from 9.7 ± 7.1 at month 1 to 13.5 ± 5.6 dB at the final check, and was weakly (r=0.33) correlated with post-operative BCVA and OCT abnormalities. CONCLUSION: long-standing metamorphopsia can occur after successful macula-off RD repair even without detectable photoreceptor disruption on OCT. Post-operative BCVA recovery weakly correlates with increasing MS, and late restoration of the photoreceptor layer may be observed.

Macular automatic fundus perimetry threshold versus standard perimetry threshold.

PURPOSE: To evaluate if retinal sensitivity threshold obtained with an automatic fundus perimeter may be compared with a standard perimeter retinal threshold. METHODS: Automatic full-threshold fundus perimetry (microperimetry) of the macular area (10 degrees grid, 37 stimulated points) was quantified with a new automatic fundus perimeter (MP1 microperimeter) in nine normal subjects (18 eyes). Retinal threshold was also quantified using an identical grid projected with a standard Octopus 101 perimeter. RESULTS: Mean threshold registered by MP1 microperimeter was 19.7+/-0.8 dB (range 16-20 dB; 4.38+/-0.96 asb, range 4-10 asb) versus 33.1+/-1.7 dB (range 27-38 dB; 0.53+/-0.22 asb, range 0.16-2 asb) obtained with Octopus perimeter. Mean SD of intraindividual variation was 0.74 dB in MP1 and 1.51 dB in Octopus. No statistically significant differences were documented between right and left eye with both instruments (p=0.64). No reliable mathematical relationship between retinal thresholds could be obtained with the two perimeters. CONCLUSIONS: Fundus perimetry is a precise, functional fundus-related technique which allows threshold determination at selected retinal points even if fixation is unstable and visual acuity is low. This is beyond the possibility of any static standard perimetry. Normal threshold values obtained with MP1 automatic microperimeter cannot be currently compared with those obtained with standard Octopus perimeter.

Peripapillary fundus perimetry in eyes with glaucoma.

AIMS: To evaluate, with fundus perimetry, the peripapillary differential light threshold (DLT) in eyes with glaucoma and ocular hypertension (OHT), and compare it with peripapillary retinal nerve fibre layer (RNFL) thickness. METHODS: 35 glaucomatous, 29 OHT and 24 control eyes were included. Peripapillary DLT at 1 degrees from the optic nerve head was quantified with fundus perimetry; peripapillary RNFL thickness was measured over the same area by optical coherence tomography. RESULTS: Mean (SD) peripapillary DLT was 19.2 (1.7), 17.6 (4.2) and 10.1 (6.9) dB in control, OHT and glaucomatous eyes, respectively (p<0.001). Mean (SD) RNFL thickness was 98.4 (35.3), 83.9 (35.1) and 55.8 (28.2) microm, respectively (p<0.001). Mean peripapillary DLT showed higher sensitivity and specificity in differentiating the three groups compared with RNFL thickness. CONCLUSION: Progressive, significant reduction of peripapillary DLT was documented in OHT and glaucomatous eyes compared with controls (p<0.001). DLT reduction parallels RNFL reduction.

In vivo detection of monosomy 3 in eyes with medium-sized uveal melanoma using transscleral fine needle aspiration biopsy.

PURPOSE: Cytogenetic prognostication of choroidal melanoma, particularly monosomy 3 detections, is limited to enucleated eyes or resected tumors. The authors developed an in vivo technique to detect monosomy 3 using transscleral fine needle aspiration biopsy (FNAB). METHODS: Eight eyes with medium-sized choroidal melanoma were included in this prospective study. A 25-gauge transscleral FNAB was performed during surgical procedure for brachytherapy, just before applying the radioactive plaque over the tumor base. Sampled material underwent fluorescence in situ hybridization (FISH) with centromeric probes for chromosome 3. Follow-up was >12 months. RESULTS: Transscleral FNAB yielded sufficient material in 7 of 8 eyes (87.5 %). Five of seven eyes had monosomy 3. No early or late complications were detected. CONCLUSIONS: This study demonstrates that medium choroidal melanomas may be safely sampled by intraoperative transscleral FNAB to detect monosomy 3 in vivo.

Reconstruction of conjunctiva with amniotic membrane after excision of large conjunctival melanoma: a long-term study.

PURPOSE: To evaluate, on a long- term basis, the role of amniotic membrane in the reconstruction of large conjunctival defects after excision of large conjunctival melanoma. METHODS: Four consecutive patients with diffuse conjunctival melanoma involving both bulbar and palpebral conjunctiva were studied. Conjunctival melanoma was completely excised (with wide clinically disease-free margins) and amniotic membrane immediately sutured to the surrounding conjunctiva and sclera to cover the conjunctival defect. Minimum follow-up was 48 months. RESULTS: Successful conjunctival surface reconstruction and physiologic fornical depth were achieved in all patients within 6 weeks. No recurrence of primary melanoma was observed during long-term follow-up. CONCLUSIONS: Amniotic membrane transplantation is an effective alternative in ocular surface repairing surgery after removal of large conjunctival tumors.

Treatment of conjunctival squamous cell carcinoma with topical 5-fluorouracil.

AIM: To evaluate the efficacy of topical 5-fluorouracil (5-FU) alone, without concurrent surgery or radiotherapy, for the treatment of conjunctival squamous cell carcinoma. METHODS: Eight patients affected by conjunctival squamous cell carcinoma (three recurrent cases, three incompletely excised, and two untreated cases) were treated with 1% 5-FU eye drops. Topical 1% 5-FU was administered four times daily for 4 weeks (one course). Clinical examination (biomicroscopy and photography) and morphological evaluation of conjunctival cytological specimens were used to monitor the efficacy of local chemotherapy, side effects, and recurrences. RESULTS: All patients showed clinical regression of conjunctival carcinoma after topical 1% 5-FU treatment. Neoplastic conjunctiva was completely replaced by normal epithelium within 3 months. Mean follow up was 27 months. One patient needed two courses of local chemotherapy for recurrent disease. An acute transient toxic keratoconjunctivitis was observed in all treated cases; it was easily controlled with topical therapy. No long term side effects were found. CONCLUSIONS: Topical 1% 5-FU is effective in the treatment of recurrent, incompletely excised, and selected untreated conjunctival squamous cell carcinomas. Topical 1% 5-FU has no major complications. This study suggests that topical conjunctival chemotherapy with 1% 5-FU may be useful, at least as adjunctive therapy, in the treatment of conjunctival squamous cell carcinoma.

Isolated brain metastasis of malignant choroidal melanoma 27 years after enucleation.

Choroidal melanoma primarily metastasizes to the liver. Isolated extrahepatic metastases have rarely been reported and they generally resulted in death within 6 months. We describe a patient who developed an isolated brain metastasis 27 years after his left eye was enucleated for choroidal melanoma. The metastasis was successfully treated with surgery and radiotherapy. The patient is alive and disease free 3 years after treatment of the metastasis. Posterior location and other clinical and morphologic characteristics of primary choroidal melanoma could explain the unusually long latency of this solitary extrahepatic metastatic disease. Lifelong surveillance to detect early signs of metastasis is mandatory for any patient treated for choroidal melanoma.

Optic atrophy as the first symptom in Hallervorden-Spatz syndrome.

A 16-year-old boy with the classic or postinfantile type of Hallervorden-Spatz syndrome is described. Bilateral optic atrophy with visual loss but without retinal changes was the only presenting symptom. Mild cognitive impairment, behavioural disturbances and insidious extrapyramidal involvement appeared later. MRI showed marked symmetrical hypointensity of the globi pallidi and substantia nigra. This new observation suggests that the occurrence of optic atrophy in a patient with Hallervorden-Spatz syndrome should be regarded as noncoincidental and stresses the importance of an accurate neurological work-up in all adolescents with any unusual form of progressive optic atrophy.

Pregnancy does not induce or worsen retinal and peripheral nerve dysfunction in insulin-dependent diabetic women.

In order to verify whether pregnancy induces or worsens diabetic retinopathy or somatic and autonomic neuropathy, 16 insulin-dependent diabetic (IDDM) pregnant women, 14 age-matched nondiabetic pregnant women, and 12 IDDM nonpregnant women matched for age and disease duration were studied. Plasma glucose, HbA1c, and fructosamine were repeatedly assayed during pregnancy. Retinopathic and neuropathic endpoints were evaluated through ophthalmoscopy, electrophysiology of left peroneal and sural nerves (motor and sensory conduction velocities), and cardiovascular autonomic tests (deep breathing, cough test, lying-to-standing). In the IDDM pregnant women, evaluations were performed three times during pregnancy and 6 months after delivery. Good metabolic control was achieved during pregnancy. At baseline, nine IDDM pregnant women did not show signs of retinopathy, and seven had nonproliferative retinopathy. Only one patient showed worsening during pregnancy, but she improved after delivery. Motor conduction velocity, significantly lower in IDDM pregnant women, progressively improved, and, in the third trimester, was not significantly different from that of nondiabetic pregnant women. At baseline, none of the IDDM pregnant women had abnormal responses to cardiovascular autonomic tests. During pregnancy, the response to deep breathing appeared temporarily reduced in all pregnant women, possibly due to lowered ventilatory excursion at the end of pregnancy. In IDDM women with minimal or no retinopathy, and subclinical or no peripheral neuropathy, pregnancy does not appear to induce or worsen these complications.

Macular function impairment in eyes with early age-related macular degeneration.

PURPOSE: To study different aspects of macular function in eyes with early age-related macular degeneration (early AMD: drusen with or without retinal pigment epithelium alterations) and normal visual acuity, to obtain a complete evaluation of macular function impairment in early AMD and to study the relationship between macular function and the ophthalmoscopic signs of early AMD. METHODS: Forty-seven subjects with early AMD and visual acuity better than 20/25 in at least one eye were studied: 34 patients had bilateral early AMD (group 1), 13 had neovascular AMD in the fellow (nonstudy) eye (group 2). Thirty-six age-matched healthy subjects were used as controls. Thirty degree stereoscopic fundus photographs and fluorescein angiography were performed to grade macular lesions. Macular recovery function, central visual field sensitivity, spatiotemporal contrast sensitivity, and the Farnsworth-Munsell 100 hue test were used to study different aspects of macular function. RESULTS: Except for color vision, all macular function tests were significantly impaired in eyes of patients with early AMD compared to those in control subjects. No functional difference was found between groups 1 and 2. The increase in drusen number negatively influenced macular recovery function. Increasing drusen confluence reduced macular recovery function as well as central visual field sensitivity and some selected spatial frequencies of spatiotemporal contrast sensitivity. Geographic atrophy of the retinal pigment epithelium and focal hyperpigmentation reduced macular recovery function and contrast sensitivity at the highest spatial frequency. CONCLUSIONS: Macular recovery function central visual field sensitivity, and spatiotemporal contrast sensitivity are adequate and reliable indicators of macular function impairment in early AMD. Macular recovery function is the test that best reflects the ophthalmoscopic characteristics of early AMD because its deterioration parallels the worsening of typical fundus lesions. Function tests are valuable in the evaluation of patients with early AMD, particularly when interventional trials are planned.

The effect of external eye irradiation on choroidal circulation.

BACKGROUND: The effect of external beam radiation therapy (teletherapy) on the choroidal circulation is poorly known. Eyes irradiated with teletherapy represent a good model to study, without confounding factors, the pathophysiologic and clinical aspects of radiation-induced chorioretinal damage. This study used fluorescein and indocyanine green choroidal angiography to investigate the late effects of external eye irradiation on the choroidal circulation. METHODS: Fluorescein angiography and indocyanine green choroidal videoangiography were performed on patients with radiation retinopathy because of external eye irradiation for orbital and paranasal sinus malignancies. Patients were divided into two groups according to the treatment field (anterior unilateral or bilateral). RESULTS: Indocyanine green angiograms showed areas of choriocapillaris hypoperfusion in all eyes-unilateral or bilateral irradiation-affected by radiation retinopathy. Late indocyanine green choroidal staining was found in five eyes (28%) of the patients who received unilateral anterior irradiation. In the same group, nine eyes (52%) had signs of choroidal precapillary occlusion and four eyes (23%) had rubeosis iridis without retinal neovascularization. One case of subfoveal choroidal neovascularization was documented in the bilateral irradiation group. CONCLUSIONS: Radiation side effects are not limited to the retinal vessels but also involve choroidal circulation. The damage to the choroid is primarily vascular, and its clinical aspects depend on the treatment fields. Anterior irradiation may be a critical factor for the appearance of unusual rubeosis iridis and neovascular glaucoma.

Macular drusen and the sensitivity of the central visual field.

Macular drusen are one of the earliest signs of age-related macular degeneration but little information is available on the functional aspects of macular area in patients with drusen. To determine if drusen are associated with changes in central visual field sensitivity, one eye of each of 35 subjects (mean age 64.9 years) with bilateral drusen and visual acuity of 1.0 (20/20) underwent automated static threshold perimetry of the central 10 degrees. 16 normal subjects (mean age 65.8 years) were used as controls. 30 degrees fundus photographs were graded in a masked fashion for the clinical characteristics of drusen: type, size and number. The mean sensitivity (MS) of the central 10 degrees was significantly lower in eyes with drusen compared to normal eyes (p = .0001). After grading drusen eyes for size (> or = 63 mu) and type (presence of soft drusen), MS significantly deteriorated when large and soft drusen were present. These results suggest that central visual field sensitivity is precociously affected in eyes with drusen and that testing central visual field sensitivity may be useful as functional parameter in long term studies on the evolution of age-related macular degeneration.

Age-related macular degeneration.

Age-related macular degeneration (AMD), a bilateral, progressive macular disease, represents the major cause of blindness among elderly people living in Western countries. Clinical features of AMD vary from the initial asymptomatic aspects, drusen and retinal pigment epithelium alterations, to severe atrophic or exudative changes in the advanced stages, characterized by the irreversible decrease of visual function. Current epidemiologic, pathogenetic and clinical data are reviewed, and the importance of the exact identification of patients at risk of evolution toward the exudative form is addressed. The therapeutic approach to AMD is also analyzed and the role of laser photocoagulation is discussed.

Orbital ectopic lacrimal gland tissue simulating a neoplasm. Report of a case with fine needle aspiration biopsy diagnosis.

A case occurred of sclerosing chronic dacryoadenitis in lobules of ectopic lacrimal gland tissue diagnosed by fine needle aspiration biopsy performed under computed tomographic guidance. This choristomatous lesion caused unilateral proptosis and clinically simulated a neoplasm. This is the first report of cytologic diagnosis of orbital ectopic lacrimal gland tissue using fine needle aspiration biopsy. The potential hazard of regarding glandular inclusions derived from inadvertent use of a needle on a normal lacrimal gland or glands as indicating metastatic neoplasms is stressed.