Novel Drug Delivery Methods and Approaches for the Treatment of Retinal Diseases.

This review discusses emerging approaches to ocular drug delivery for retinal diseases. Intravitreal injections have proven to be an effective, safe, and commonly used drug delivery method. However, the optimal management of chronic retinal diseases requires frequent intravitreal injections over extended periods of time. Although this can be achieved in a clinical trial environment, it is difficult to replicate in routine clinical practice. In addition, frequent treatment increases the risk of complications, incurs more costs, and increases the treatment burden for patients and caregivers. Given the aging global population and diabetes pandemic, there is an urgent need for drug delivery methods that support more durable retinal therapy while maintaining the efficacy and safety of currently available intravitreal therapies. Several innovative drug delivery methods are currently being investigated. These include sustained-release implants and depots using prodrugs, microparticles, and hydrogels, surgically implanted reservoirs, gene therapy via submacular injections or suprachoroidal injections, as well as topical and systemic therapies.

Microperimetry in Retinal Diseases.

Retinal microperimetry (MP) is a procedure that assesses the retinal sensitivity while the fundus is directly observed, and an eye tracker system is active to compensate for involuntary eye movements during testing. With this system, the sensitivity of a small locus can be accurately determined, and it has become an established ophthalmic test for retinal specialists. Macular diseases are characterized by chorioretinal changes; therefore, the condition of the retina and choroid requires careful and detailed evaluations to perform effective therapy. Age-related macular degeneration is a representative retinal disease in which the macular function has been evaluated by the visual acuity throughout the course of the disease process. However, the visual acuity represents the physiological function of only the central fovea, and the function of the surrounding macular area has not been sufficiently evaluated throughout the different stages of the macula disease process. The new technique of MP can compensate for such limitations by being able to test the same sites of the macular area repeatedly. This is especially useful in the recent management of age-related macular degeneration or diabetic macular edema during anti-vascular endothelial growth factor treatments because MP can assess the effectiveness of the treatment. MP examinations are also valuable in diagnosing Stargardt disease as they can detect visual impairments before any abnormalities are found in the retinal images. The visual function needs to be carefully assessed along with morphologic observations by optical coherence tomography. In addition, the assessment of retinal sensitivity is useful in the presurgical or postsurgical evaluations.

Scalpel sign: Dorsal thoracic arachnoid web, thoracic arachnoid cyst and ventral cord herniation.

The "Scalpel sign" is a radiological sign which can be identified on magnetic resonance imaging and indicates dorsal compression of the spinal cord [1]. Prior descriptions of a "Scalpel sign" have been reported in the literature and the awareness and identification of this pathognomonic sign may aid in the rapid diagnosis and treatment of patients with dorsal arachnoid web, dorsal arachnoid cyst or ventral cord herniation. We describe 3 cases which highlight these rare conditions for which this sign is pathognomonic and summarize the pertinent literature related to these disorders [1,2].

Gitelman syndrome and ectopic calcification in the retina and joints.

Gitelman syndrome is a rare inherited renal tubular disorder with features that resemble thiazide use, including a hypokalemic metabolic alkalosis, hypomagnesemia, hypocalciuria and a low or normal blood pressure, hyperreninemia and hyperaldosteronism. Treatment is primarily correction of the potassium and magnesium levels. The diagnosis is confirmed with genetic testing but Gitelman syndrome is often not suspected. However, the association with ectopic calcification in the retina, blood vessels and chondrocalcinosis in the joints is a useful pointer to this diagnosis. Bilateral symmetrical whitish deposits of calcium pyrophosphate are visible superotemporally on ophthalmoscopy and retinal photography but are actually located beneath the retina in the sclerochoroid. Optical coherence tomography is even more sensitive for their detection. These deposits increase in size with time, but the rate of progression slows with long-term correction of the hypomagnesemia. Calcification may be complicated by atrophy of the overlying retina and visual loss. The deposits often correlate with ectopic calcification in the aorta and coronary and cerebral vessels. Chondrocalcinosis occurs in the large joints such as the knees. Ectopic calcification in Gitelman syndrome indicates the need for more aggressive management of Mg levels. Calcification is much less common in Bartter syndrome, which itself is rarer and associated less often with hypomagnesemia.