Non-viral ocular gene therapy: potential ocular therapeutic avenues.

Non-viral vectors for potential gene replacement and therapy have been developed in order to overcome the drawbacks of viral vectors. The diversity of non-viral vectors allows for a wide range of various products, flexibility of application, ease of use, low-cost of production and enhanced "genomic" safety. Using non-viral strategies, oligonucleotides (ODNs) can be delivered naked (less efficient) or entrapped in cationic lipids, polymers or peptides forming slow release delivery systems, which can be adapted according to the organ targeted and the therapy purposes. Tissue and cell internalization can be further enhanced by changing by physical or chemical means. Moreover, a specific vector can be selected according to disease course and intensity of manifestations fulfilling specific requirements such as the duration of drug release and its level along with cells and tissues specific targeting. From accumulating knowledge and experience, it appears that combination of several non-viral techniques may increase the efficacy and ensure the safety of these evolving and interesting gene therapy strategies.

Le xeroderma pigmentosum et ses manifestations oculaires. A propos du premier cas camerounais [Xeroderma pigmentosum and its ocular manifestations. The first case in Cameroon].

We report a case of xeroderma pigmentosum in a 9-year-old back Cameroonian boy. The diagnosis was based on typical clinical presentation of the disease: cutaneous atrophy, hypepigmented macules, and areas of depigmentation on sun exposed regions of the skin. Multiple tumoral lesions were localized on the head. Ocular findings were also present: conjunctival hyperemia, peripheral corneal opacification. Excision of the tumors and potoprotection was proposed for this patient. The role of tribal black African marriage traditions in disease transmission is discussed.

Acurácia da ultrassonografia e da avaliação comportamental na determinação das características funcionais de estruturas ovarianas císticas

O objetivo deste trabalho foi avaliar a acurácia da ultrassonografia e da sintomatologia em determinar características funcionais de estruturas ovarianas císticas. Em 51 vacas Girolando sem corpo lúteo, foram avaliados: presença ou ausência de tecido luteal na parede do folículo; concentrações séricas de progesterona (P4); e sinais comportamentais dos animais (anestro ou ninfomania). As concentrações plasmáticas de P4 foram consideradas como padrão ouro. A avaliação ultrassonográfica foi um método preciso (82,4%) para diagnosticar o tipo de cisto folicular. O anestro está relacionado à presença de cisto luteinizado e à elevada P4. Os cistos não luteinizados são frequentemente encontrados em animais com baixa P4, que apresentam comportamento de anestro ou ninfomania.

Spectrum of ocular digoxin toxicity in the elderly: A case report

Introduction: We report a case of digoxin intoxication with severe visual symptoms. Patients (or Materials) and Methods: Digoxin 0.25 mg QD for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 mL/min. Within 2 to 3 weeks, she developed nausea, vomiting, and dysphagia, and began complaining of snowy and blurry vision, photopsia, dyschromatopsia, aggravated bedtime visual and proprioceptive illusions (she felt as being on a boat), and colored hallucinations. She consulted her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, impaired autonomy led her to be admitted to the emergency department. Results: Digoxin intoxication was confirmed by a high plasma level measured on admission (5.7 μg/L; reference range, 0.8-2 μg/L). After stopping digoxin, general symptoms resolved in a few days, but visual symptoms persisted. Ophtalmologic care and follow-up diagnosed digoxin intoxication superimposed on pre-existing left eye (LE) cataract, dry age-related macular degeneration (DMLA), and Charles Bonnet syndrome. Visual acuity was 0.4 (right eye, RE) and 0.5 (LE). Ocular fundus was physiologic except for bilateral dry DMLA. Dyschromatopsia was confirmed by poor results on Ishihara test (1/13 OU). Computerized visual field results revealed nonspecific diffuse alterations. Full-field electroretinogram (ERG) showed moderate diffuse rod and cone dysfunction. Visual symptoms progressively improved over the next 2 months, but ERG did not. Complete resolution was not expected due to the pre-existing eye disease. The patient was finally discharged home after a 5-week hospital stay. Conclusion: Digoxin intoxication can go unrecognized by clinicians, even in a typical presentation. The range of potential visual symptoms is far greater than isolated xanthopsia (yellow vision) classically described in textbooks. Newly introduced drugs and all symptoms must be actively sought after, because they significantly affect quality of life and global functioning, especially in the elderly population, most liable not to mention them.

Ultrasound assessment of ocular vascular effects of repeated intravitreal injections of ranibizumab for wet age-related macular degeneration.

PURPOSE: Determine the effect of repeated intravitreal injections of ranibizumab (0.5 mg; 0.05 ml) on retrobulbar blood flow velocities (BFVs) using ultrasound imaging quantification in twenty patients with exudative age-related macular degeneration treated for 6 months. METHODS: Visual acuity (ETDRS), central macular thickness (OCT), peak-systolic, end-diastolic and mean-BFVs in central retinal (CRA), temporal posterior ciliary (TPCA) and ophthalmic (OA) arteries were measured before, 2 days, 3 weeks and 6 months after the first injection. Patients were examined monthly and received 1-5 additional injections depending on ophthalmologic examination results. RESULTS: Six months after the first injection, a significant increase in visual acuity 50.9 ± 25.9 versus 44.4 ± 21.7 (p < 0.01) and decrease in mean central macular thickness 267 ± 74 versus 377 ± 115 μm (p < 0.001) were observed compared to baseline. Although mean-BFVs decreased by 16%±3% in CRA and 20%±5% in TPCA (p < 0.001) 2 days after the first injection, no significant change was seen thereafter. Mean-BFVs in OA decreased by 19%±5% at week 3 (p < 0.001). However, the smallest number of injections (two injections) was associated with the longest time interval between the last injection and month 6 (20 weeks) and with the best return to baseline levels for mean-BFVs in CRA, suggesting that ranibizumab had reversible effects on native retinal vascular supply after its discontinuation. Moreover, a significant correlation between the number of injections and percentage of changes in mean-BFVs in CRA was observed at month 6 (R = 0.74, p < 0.001) unlike TPCA or OA. CONCLUSION: Ranibizumab could impair the native choroidal and retinal vascular networks, but its effect seems reversible after its discontinuation.

Transient ocular motor nerve palsies associated with presumed cranial nerve schwannomas.

BACKGROUND: Cranial nerve schwannomas are radiologically characterized by nodular cranial nerve enhancement on magnetic resonance imaging (MRI). Schwannomas typically present with gradually progressive symptoms, but isolated reports have suggested that schwannomas may cause fluctuating symptoms as well. METHODS: This is a report of ten cases of presumed cranial nerve schwannoma that presented with transient or recurring ocular motor nerve deficits. RESULTS: Schwannomas of the third, fourth, and fifth nerves resulted in fluctuating deficits of all 3 ocular motor nerves. Persistent nodular cranial nerve enhancement was present on sequential MRI studies. Several episodes of transient oculomotor (III) deficts were associated with headaches, mimicking ophthalmoplegic migraine. CONCLUSIONS: Cranial nerve schwannomas may result in relapsing and remitting cranial nerve symptoms.

Spectrum of digoxin-induced ocular toxicity: a case report and literature review.

BACKGROUND: Digoxin intoxication results in predominantly digestive, cardiac and neurological symptoms. This case is outstanding in that the intoxication occurred in a nonagenarian and induced severe, extensively documented visual symptoms as well as dysphagia and proprioceptive illusions. Moreover, it went undiagnosed for a whole month despite close medical follow-up, illustrating the difficulty in recognizing drug-induced effects in a polymorbid patient. CASE PRESENTATION: Digoxin 0.25 mg qd for atrial fibrillation was prescribed to a 91-year-old woman with an estimated creatinine clearance of 18 ml/min. Over the following 2-3 weeks she developed nausea, vomiting and dysphagia, snowy and blurry vision, photopsia, dyschromatopsia, aggravated pre-existing formed visual hallucinations and proprioceptive illusions. She saw her family doctor twice and visited the eye clinic once until, 1 month after starting digoxin, she was admitted to the emergency room. Intoxication was confirmed by a serum digoxin level of 5.7 ng/ml (reference range 0.8-2 ng/ml). After stopping digoxin, general symptoms resolved in a few days, but visual complaints persisted. Examination by the ophthalmologist revealed decreased visual acuity in both eyes, 4/10 in the right eye (OD) and 5/10 in the left eye (OS), decreased color vision as demonstrated by a score of 1/13 in both eyes (OU) on Ishihara pseudoisochromatic plates, OS cataract, and dry age-related macular degeneration (ARMD). Computerized static perimetry showed non-specific diffuse alterations suggestive of either bilateral retinopathy or optic neuropathy. Full-field electroretinography (ERG) disclosed moderate diffuse rod and cone dysfunction and multifocal ERG revealed central loss of function OU. Visual symptoms progressively improved over the next 2 months, but multifocal ERG did not. The patient was finally discharged home after a 5 week hospital stay. CONCLUSION: This case is a reminder of a complication of digoxin treatment to be considered by any treating physician. If digoxin is prescribed in a vulnerable patient, close monitoring is mandatory. In general, when facing a new health problem in a polymorbid patient, it is crucial to elicit a complete history, with all recent drug changes and detailed complaints, and to include a drug adverse reaction in the differential diagnosis.

Ocular adnexal (orbital) solitary fibrous tumor: nuclear STAT6 expression and literature review.

PURPOSE: To report the clinico-pathological features of solitary fibrous tumor occurring in the ocular adnexa (OA) in a single center. To assess the presence of NAB2-STAT6 genes fusion in OA solitary fibrous tumor detected by nuclear overexpression of STAT6. METHODS: Retrospective study including orbital and OA solitary fibrous tumors treated between 2006 and 2014 in our center. The clinical, radiological, and histopathological findings were evaluated. STAT6 expression was assessed by immunohistochemistry. RESULTS: Five patients were identified and presented with a chronic OA mass. The tumors were radiologically well delimited, highly vascularized and without bone erosion. All the patients underwent complete surgical excision. Pathological examination confirmed solitary fibrous tumor in all cases. All tumors demonstrated a nuclear expression of STAT6. There were no recurrences, with a mean follow-up of 5 years after surgery. Our review demonstrated that proptosis was the most common presentation occurring in 60 % of the cases. In the ocular adnexa, adverse histological criteria were found in 19.7 % of the tumors, and recurrences were observed in 48 % of these cases. Thirty-six percent of patients presented at least one local recurrence, and metastastic spread was found in 2.4 % of the cases. Tumor-related death was described in two cases. CONCLUSION: Ocular adnexal SFT are rare and usually present as a chronic orbital mass with proptosis. In the OA, solitary fibrous tumor demonstrates STAT6 nuclear expression, as documented in other locations. Recurrences are unusual and metastasis exceptional. Initial surgical resection should be complete in order to avoid recurrence.

Proptose ocular como manifestação clínica de tumores malignos extra-orbitários: estudo pela tomografia computadorizada

Doenças sistêmicas, doenças orbitárias primárias e lesões extra-orbitárias com extensão secundária para a órbita podem causar proptose ocular. Foram estudados, por tomografia computadorizada, 11 pacientes com proptose ocular causada por tumores malignos extra-orbitários, sem qualquer tratamento prévio do tumor. Houve predomínio de neoplasias não-epiteliais (82%), tendo sido três rabdomiossarcomas (27%) e três linfomas não-Hodgkin (27%). Outros sarcomas estiveram presentes em dois casos (18%), seguidos por linfoma de Burkitt (9%), carcinoma epidermóide (9%) e carcinoma pouco diferenciado (9%). Nove tumores (82%) tiveram origem nas cavidades sinonasais, a maioria (cinco casos) com origem no seio etmoidal. Proptose ocular foi a única alteração oftálmica em quatro casos (36%), e um paciente teve proptose ocular bilateral como único sinal da doença. Dezessete órbitas foram acometidas pelos 11 tumores, já que seis pacientes tiveram comprometimento orbitário tumoral bilateral. Os tumores se estenderam às órbitas preferencialmente através da parede óssea orbitária (16 órbitas; 94%). Das 17 órbitas comprometidas, a maioria (59%) teve todos os compartimentos lesados. Em 16 órbitas o tumor apresentou situação extraconal. À tomografia computadorizada, proptose ocular esteve presente em 15 das 17 órbitas (88%), tendo sido bilateral em quatro casos (oito órbitas). Houve predomínio de proptose ocular grau 2 à tomografia computadorizada (sete pacientes; 47%). Um total de 44 regiões crânio-faciais foi comprometido, além da órbita e do sítio de origem da neoplasia, indicando a grande extensão loco-regional desses tumores no momento do diagnóstico.

Tratamento conservador ocular dos melanomas de coróide com braquiterapia utilizando placas de iodo-125

OBJETIVO: Avaliar, retrospectivamente, o resultado do tratamento conservador do melanoma de coróide, por meio de braquiterapia, usando placas episclerais de iodo-125 (modelo 6711, Amershan). MATERIAIS E MÉTODOS: Foram avaliados 49 pacientes portadores de melanoma de coróide tratados no Hospital do Câncer, São Paulo, SP, de março de 2001 a janeiro de 2003. Os seguintes parâmetros foram analisados e correlacionados ao controle local e sobrevida: sexo, idade, dimensões da lesão, tempo de tratamento e doses no ápice e base das lesões. RESULTADOS: Com diâmetro máximo da base do tumor de 17 mm e altura máxima de 12 mm, observamos que as doses na base do tumor variaram de 213 a 463 Gy (mediana de 347 Gy) e no ápice, de 51 a 250 Gy (mediana de 91 Gy). As taxas de preservação ocular, sobrevida livre de doença e conservação ocular, atuariais em dois anos, foram de 96%, 93,5% e 96,3%, respectivamente. Através de análise univariada, o único fator prognóstico para controle local nesta análise foi a altura do tumor menor que 6 mm (p = 0,0348). CONCLUSÃO: A braquiterapia levou a uma taxa bastante satisfatória de controle local, confirmando que a altura do tumor é um dos fatores prognósticos importantes desse parâmetro.