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1.
Bioorg Med Chem Lett ; 28(10): 1870-1873, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29661534

ABSTRACT

Age-related macular degeneration (AMD) as well as other choroidal diseases, demand novel therapeutic methods. Photodynamic therapy (PDT), which uses light and photosensitizer (PS) to cause specific vascular occlusion in the macula, is an interesting alternative. The only drug approved for the PDT treatment of AMD (Verteporfin) has a natural tendency to aggregate, demanding an expensive separation procedure during purification. We report a novel and affordable PS that is intrinsically protected against aggregation, the Monomeric Chlorin at High Concentration (MCHC-Chlorin), whose liposomal formulation was developed to provoke effective photodynamic action on the choroidal vasculature. Our report starts by stablishing the conditions to allow the efficient synthesis of MCHC-Chlorin in high yields (92%). We then tested the light stimulated occlusion of choriocapillary vessels in rabbit's eyes induced by the two MCHC-Chlorin isomers, which are directly obtained from the synthetic route. The PS formulation was infused in the rabbit's ear vein and eyes were immediately irradiated at 650 nm. Indirect ophthalmoscopy, fundus photography, fluorescein angiography and histopathological evaluations were used to evaluate levels of photo-thrombosis and collateral damage. Choriocapillary occlusion was achieved in all treated rabbits' eyes, while retina and sclera were completely preserved. There was no photochemical reaction in none of the eyes that received LASER without PS. Both MCHC-Chlorin isomers were separately tested and exhibited similar positive results with no systemic toxicity. Therefore, PDT occurred equally well in all treated eyes and none of the controls showed any effect in the ophthalmological exams. MCHC-Chlorin offers great potential and should be further studied as an alternative drug for choroidal diseases.


Subject(s)
Photosensitizing Agents/chemistry , Porphyrins/chemistry , Animals , Choroid/pathology , Choroid Diseases/drug therapy , Choroid Diseases/etiology , Choroid Diseases/veterinary , Eye/diagnostic imaging , Eye/radiation effects , Fluorescein Angiography , Isomerism , Lasers , Light , Liposomes/chemistry , Photochemotherapy , Photosensitizing Agents/therapeutic use , Porphyrins/therapeutic use , Rabbits , Retina/pathology
2.
Ophthalmic Surg Lasers Imaging Retina ; 49(1): 70-75, 2018 01 01.
Article in English | MEDLINE | ID: mdl-29304271

ABSTRACT

In a prospective case series of patients with Blau-Jabs syndrome (BJS) conducted in the Ophthalmology Department/Federal University of Sao Paulo, seven patients with clinical and ophthalmologic manifestations of the disease and a positive genetic test result for the presence of a mutation in the CARD15/NOD2 gene were followed for a minimal period of 1 year. All patients had uveitis, five had nummular corneal subepithelial opacities, and four had multifocal choroiditis. Oral prednisolone was administered to all patients; inflammation was controlled in six patients with at least one immunosuppressive drug. Infliximab (Remicade; Janssen Pharmaceuticals, Beerse, Belgium) and etanercept (Enbrel; Amgen, Thousand Oaks, CA) were used to treat two cases refractory to the anti-inflammatory drugs. A subconjunctival dexamethasone implant (Ozurdex; Allergan, Irvine, CA) and a periocular injection of triamcinolone were used in one case to achieve inflammation control. Six patients achieved a visual acuity of 20/25 or better. The authors conclude that periocular treatment with steroid injections might be effective adjuvant therapy to control ocular inflammation. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:70-75.].


Subject(s)
Anterior Eye Segment/diagnostic imaging , Arthritis/diagnosis , Genetic Testing/methods , Immunosuppressive Agents/therapeutic use , Synovitis/diagnosis , Tertiary Care Centers , Uveitis/diagnosis , Adolescent , Adult , Arthritis/drug therapy , Arthritis/genetics , Child , DNA/genetics , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Male , Microscopy, Acoustic , Mutation , Nod2 Signaling Adaptor Protein/genetics , Nod2 Signaling Adaptor Protein/metabolism , Prospective Studies , Sarcoidosis , Synovitis/drug therapy , Synovitis/genetics , Uveitis/drug therapy , Uveitis/genetics , Young Adult
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