Daryl E. Kurz

Novel approaches for retinal drug delivery.

Novel methods of ophthalmic drug delivery are being developed to facilitate treatment of a variety of eye diseases. Pharmaceuticals administered intravitreally are able to bypass the blood-ocular barrier to achieve constant therapeutic levels in the eye, while minimizing systemic side effects. Sustained-release intravitreal implants are being developed to enhance further the intravitreal route of administration. Liposomes, microscopic vesicles with a membrane-like lipid bilayer surrounding an aqueous compartment, are being developed to incorporate a wide variety of drug molecules, proteins, nucleotides, and even plasmids giving them great potential for use in ophthalmology. Biodegradable scleral plugs containing pharmaceuticals have the advantage of biodegradability and the ability to fit in a relatively small diameter of 1 mm. Conjugate drugs, which are covalently linked, decrease drug solubility, which increases their half-life and also limits the amount of active drug present at a given time. Viral vectors have been investigated in the delivery of genetic material to the posterior segment of the eye. Retrovirus, adenovirus, adenoma-associated virus, herpes virus, and lentivirus have been investigated for gene transfer to the retina. Finally, iontophoresis, a method of drug delivery typically involving the application of low electric currents to drive molecules across barriers, such as skin, is being explored for ophthalmic applications.

Treatment of retinal and choroidal degenerations and dystrophies: current status and prospects for gene-based therapy

Inherited retinal and choroidal degenerations account for a significant portion of blindness in children and young adults. This article reviews the current status and future prospects for the treatment of these disorders. Current treatment strategies include nutritional intervention for gyrate atrophy of the choroid and retina with hyperornithinemia, abetalipoproteinemia, and Refsums disease, as well as vitamin A supplementation for retinitis pigmentosa. Future therapeutic prospects include gene therapy for both recessive and dominant disease, secondary gene-based therapies, such as pharmaceutic gene product replacement and treatment with survival factors, anti-apoptotic agents, and calcium blockers, and, finally, stem cell therapy.

Lack of Consensus in the Diagnosis and Treatment for Ocular Tuberculosis among Uveitis Specialists

Abstract Purpose: To assess the approach of specialists to ocular tuberculosis (TB). Methods: The American Uveitis Society (AUS) Listserv was surveyed using two clinical cases and general questions. Results: Of 196 members, 87 responded (44.4%), of whom 64 were affiliated with practices in North America, while 23 were outside of North America. The survey provided normative data on how physicians evaluate patients with uveitis as well as opinions about ocular TB. Responses varied widely on such issues as (1) the pretest probability that a patient with granulomatous panuveitis had TB uveitis (range 1–75%) or that a patient with a risk factor for TB had ocular TB (range 0–90%); (2) the optimal duration of anti-TB therapy; and (3) whether therapy should be discontinued after 2 months in nonresponders. Conclusions: Consensus is lacking among uveitis specialists for the diagnosis or management of ocular TB.

Genetics of uveitis

Uveitis phenotypes can differ substantially, and most uveitis diseases are considered polygenic with complex inheritance patterns. When considering the genetics of these diseases, common threads can be identified. For example, in virtually every polygenic disease studied, there exists an HLA genetic association. This association can be strong, such as the associations of HLA-B27 with AAU and HLA-A29 with BSCR; or it can be more subtle, involving several HLA genes or a combination of HLA genes that compose specific haplotypes. In many of these conditions, it is hypothesized that genes other than classic MHC genes but located at the MHC locus may be important susceptibility genes. Genome-wide scans and other genetic methods are becoming increasingly successful in identifying genetic loci and candidate genes in many inflammatory disorders that have an uveitic component. It will be important to test these findings as uveitis-specific genetic factors. Therefore, the burgeoning understanding of the human genome promises to result in new insight into the pathogenesis of uveitis.

Idiopathic Retinal Vasculitis, Aneurysms, and Neuroretinitis in a Patient With Antiphospholipid Syndrome

genetic evaluation in any child with suspected genetically controlled retinal pathology. In the updated classification system for CXLRS inclusive of OCT findings, all 4 subtypes demonstrate foveal cystic schisis. Although this patient has multiple features of CXLRS, his lack of this critical finding places him outside this previously described classification system. It has been observed that children with CXLRS may not have clinical foveal changes at birth, but they usually manifest by age 8 years in our experience. The clinical picture of this case is somewhat of an outlier. This case may represent a fifth type of CXLRS with peripheral schisis and no associated macular lamellar schisis or foveal cystic schisis.

Effects of twice-daily topical difluprednate 0.05% emulsion in a child with pars planitis.

Purpose: To report the effects of twice-daily difluprednate in a child with pars planitis (PP). Design/methods: Case report. Results: PP was controlled with topical difluprednate for 1 year. Then an atypical pattern of steroid response—delayed, relatively sudden onset of recalcitrant ocular hypertension (OHT)—and posterior subcapsular cataract (PSC) formation necessitated alternative treatment. Conclusion: Although not a standard treatment, in select cases of PP topical difluprednate therapy could be a useful short-term treatment option while alternative treatments are considered or immunosuppressive agents build to therapeutic levels. Ophthalmologists must be aware of the potential for delayed onset of serious complications when using difluprednate.

Macular hole closure and visual improvement with topical nonsteroidal treatment.

technique were not explained. Liquid nitrogen cryotherapy has been proven to be safe and effective for conjunctival malignant neoplasms, and it also appears to be efficacious in the treatment of other ocular conditions, including benign conjunctival vascular tumors, advancing wavelike epitheliopathy, superior limbic keratoconjunctivitis, pterygia, and conjunctival amyloidosis. Based on this case series, liquid nitrogen cryotherapy could be considered an effective surgical alternative in the treatment of conjunctival lymphangiectasia. Repeat cryotherapy may be indicated should recurrent lymphangiectasia occur.

An old crone finds a new home: Crohn's disease and pars planitis.

Acknowledgements: Financial support was provided by Research to Prevent Blindness and the Stan and Madelle Rosenfeld Family Trust. The case report deserves a limited place in medical literature and didactics. Learning from an individual experience is fraught with danger; what is truly causally related and what represents a chance occurrence? How safe is it to extrapolate from an n of 1? In issue 1 of this volume, Gorroño-Echebarria and colleagues report a patient who has uveitis characterized by pars plana exudates, sacroiliitis, and biopsyproven bowel inflammation compatible with Crohn’s disease. Is this an oddity that should be filed away in a catalog of medical curiosities or is this a report with take-home lessons? We believe that this case report can serve as a virtual textbook about uveitis; it is a launching pad for a discussion about nomenclature, treatment, differential diagnosis, laboratory test selection, and pathogenesis. The process of evaluating a patient with uveitis begins with classifying the disease. Through a medical history, a thorough ophthalmic examination, and selected laboratory tests, the physician tries to place the uveitis into a specific niche. Gorroño-Echebarria and colleagues describe a 27-year-old female with bilateral anterior uveitis in association with nongranulomatous keratic precipitates, extensive posterior synechiae, normal intraocular pressure, and pars plana exudates.We are not told whether the inflammation began suddenly or insidiously; we do not know whether the inflammation resolves completely between episodes. By itself, this presentation is nonspecific; it could, for example, be compatible with sarcoidosis or so-called idiopathic disease. Some ophthalmologists would label this presentation pars planitis or intermediate uveitis because of the presence of a pars plana exudate. Other ophthalmologists would argue that typical or classical pars planitis is not associated with extensive posterior synechiae. To some purists, pars planitis is a specific condition with an insidious onset, no synechiae, chronic duration, and, of course, pars plana exudates. Bilaterality, macular edema, and peripheral periphlebitis are wellrecognized associations. This classical presentation is rarely accompanied by a systemic illness, except multiple sclerosis on occasion. While some experts consider pars plana exudates necessary and sufficient to

A Unique Case of Autoimmune Retinopathy Associated with Anti-Alpha-Enolase Antibodies

Background. We report a case of autoimmune retinopathy associated with anti-alpha-enolase antibodies with unique manifestations. Methods. A case report. Results. A 30-year-old male experienced recurrent, primarily peripheral visual field disturbances and minimal photopsia, with interval symptom resolution. Fundus changes subsequently developed in areas corresponding to the previous visual field symptoms. Electroretinogram showed bilaterally symmetric abnormalities of light-adapted responses and suggested loss of photoreceptor function. Only anti-alpha-enolase antibodies were detected on Western blot. Our patient noted cutaneous symptoms at the time of both episodes of visual symptoms, but not in the interim. Biomicroscopy revealed subtle small reddish spots in areas of the peripheral retina corresponding to the areas of the patients visual field where he noted symptoms. To our knowledge these reddish spots have not been reported in autoimmune retinopathy and may clinically support in vitro and in vivo evidence that anti-alpha-enolase antibodies may target photoreceptors. Conclusions. Our patient demonstrates some unique features adding to the known characteristics of autoimmune retinopathy associated with anti-alpha-enolase antibodies. As more cases are reported, further understanding of the features and pathophysiology of this rare condition will hopefully be elucidated.