Pharmacotherapy of retinal disease with visual cycle modulators.

Introduction: Pharmacotherapy with visual cycle modulators (VCMs) is under investigation for retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), Stargardt macular dystrophy (SMD) and nonexudative age-related macular degeneration (AMD), all blinding diseases that lack effective treatment options.

Areas Covered: The authors review investigational VCMs, including oral retinoids, 9-cis-retinyl-acetate (zuretinol) and 9-cis-β-carotene, which restore 11-cis-retinal levels in RP and LCA caused by LRAT and RPE65 gene mutations, and may improve visual acuity and visual fields. Therapies for SMD aiming to decrease accumulation of toxic Vitamin A dimers and lipofuscin in the retina and retinal pigment epithelium (RPE) include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120.

Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema: A DRCR Network Phase 2 Randomized Clinical Trial.

Importance: Some eyes have persistent diabetic macular edema (DME) following anti-vascular endothelial growth factor (anti-VEGF) therapy for DME. Subsequently adding intravitreous corticosteroids to the treatment regimen might result in better outcomes than continued anti-VEGF therapy alone.

Objective: To compare continued intravitreous ranibizumab alone with ranibizumab plus intravitreous dexamethasone implant in eyes with persistent DME.

Gene therapy for inherited retinal and optic nerve degenerations.

Introduction: The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight blood-ocular barrier, the ability to non-invasively monitor for functional and anatomic outcomes, as well as its relative immune privileged state.Vectors currently used in IRD clinical trials include adeno-associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV are non-integrating, while lentivirus integrate into the host cell genome, and have a larger transgene capacity.

The acute and chronic effects of intravitreal anti-vascular endothelial growth factor injections on intraocular pressure: A review.

The acute and chronic effects of repeated intravitreal antivascular endothelial growth factor (VEGF) injections on intraocular pressure have not been fully characterized, and the development of sustained ocular hypertension could adversely affect patients who are at risk of glaucomatous optic neuropathy. As expected, volume-driven, acute ocular hypertension immediately follows intravitreal injection, but this pressure elevation is generally transient and well tolerated. Several medications have been investigated to limit acute ocular hypertension following anti-VEGF therapy, but the benefits of pretreatment are not conclusive.

Emerging vascular endothelial growth factor antagonists to treat neovascular age-related macular degeneration.

Evolving anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) include long acting agents, combination strategies involving new pathways, topical agents, sustained-release, and genetic therapy strategies. Areas covered: Brolucizumab and abicipar pegol have smaller molecular size, facilitating higher concentrations and potentially longer duration than current anti-VEGF agents. Agents being combined with anti-VEGFs include OPT-302 (to inhibit VEGF-C and VEGF-D); pegpleranib and rinucumab (to inhibit platelet derived growth factor, PDGF - but both failed to show consistently improved visual outcomes compared to anti-VEGF monotherapy); and RG7716, ARP-1536 and nesvacumab (to activate the Tie-2 tyrosine kinase receptor, which reduces permeability).

Gene therapy for age-related macular degeneration.

In neovascular age related macular degeneration (nAMD), gene therapy to chronically express anti-vascular endothelial growth factor (VEGF) proteins could ameliorate the treatment burden of chronic intravitreal therapy and improve limited visual outcomes associated with 'real world' undertreatment. Areas covered: In this review, the authors assess the evolution of gene therapy for AMD. Adeno-associated virus (AAV) vectors can transduce retinal pigment epithelium; one such early application was a phase I trial of AAV2-delivered pigment epithelium derived factor gene in advanced nAMD.

LEAN SIX SIGMA TECHNIQUES TO IMPROVE OPHTHALMOLOGY CLINIC EFFICIENCY.

Purpose: Ophthalmologists serve an increasing volume of a growing elderly population undergoing increasingly complex outpatient medical care, including extensive diagnostic testing and treatment. The resulting prolonged patient visit times ("patient flow times") limit quality, patient and employee satisfaction, and represent waste. Lean Six Sigma process improvement was used in a vitreoretinal practice to decrease patient flow time, demonstrating that this approach can yield significant improvement in health care.

Induced pluripotent stem cell-based therapy for age-related macular degeneration.

In age-related macular degeneration (AMD), stem cells could possibly replace or regenerate disrupted pathologic retinal pigment epithelium (RPE), and produce supportive growth factors and cytokines such as brain-derived neurotrophic factor.  Induced pluripotent stem cells (iPSCs)-derived RPE was first subretinally transplanted in a neovascular AMD patient in 2014. Areas covered: Induced PSCs are derived from the introduction of transcription factors to adult cells under specific cell culture conditions, followed by differentiation into RPE cells.

Therapeutic Options in Refractory Diabetic Macular Oedema.

Diabetic macular oedema (DMO) results from alterations of several biochemical pathways in diabetic eyes. Centre-involving DMO is an important cause of visual loss in diabetes. Anti-vascular endothelial growth factor agents are now the mainstay of centre-involving DMO treatment.

EFFICACY OF DEXAMETHASONE INTRAVITREAL IMPLANT FOR REFRACTORY MACULAR EDEMA CAUSED BY RETINAL VEIN OCCLUSION.

Purpose: To investigate efficacy of dexamethasone intravitreal (DEX) implant in treating refractory macular edema caused by retinal vein occlusion.

Methods: Retrospective chart review.

Results: Twenty-two eyes with refractory macular edema caused by retinal vein occlusion were treated with a mean of 2.

PROSPECTIVE RANDOMIZED SUBJECT-MASKED STUDY OF INTRAVITREAL BEVACIZUMAB MONOTHERAPY VERSUS DEXAMETHASONE IMPLANT MONOTHERAPY IN THE TREATMENT OF PERSISTENT DIABETIC MACULAR EDEMA.

Purpose: To compare intravitreal bevacizumab monotherapy with intravitreal dexamethasone delayed delivery system monotherapy for persistent diabetic macular edema.

Methods: Single-center, randomized, subject-masked study of eyes with persistent diabetic macular edema, defined as central subfield thickness (CST) >340 μm despite ≥3 anti-vascular endothelial growth factors injections within 5 months. The intravitreal bevacizumab monotherapy (n = 23 eyes) and delayed delivery system monotherapy (n = 27 eyes) groups received treatments q1month and q3months, respectively.

INTRAOCULAR PRESSURE IN PATIENTS WITH DIABETIC MACULAR EDEMA TREATED WITH DEXAMETHASONE INTRAVITREAL IMPLANT IN THE 3-YEAR MEAD STUDY.

Purpose: To evaluate the occurrence, management, and clinical significance of increases in intraocular pressure (IOP) in patients with diabetic macular edema treated with dexamethasone intravitreal implant (DEX implant).

Methods: Randomized, multicenter, 3-year, Phase III study. Patients (N = 1,048) with diabetic macular edema were randomized to DEX implant 0.

Treatment strategies for refractory diabetic macular edema: switching anti-VEGF treatments, adopting corticosteroid-based treatments, and combination therapy.

Introduction: The pathophysiology of diabetic macular edema (DME) is complex, involving vascular endothelial growth factor (VEGF) and other inflammatory mediators. DME is currently treated first-line with intravitreal anti-VEGF treatments, though some cases are refractory to multiple anti-VEGF treatments.

Areas Covered: This article examines the evolution of treatment practices for DME, with discussion of the recent studies that guide treatment for refractory cases of DME.

RANIBIZUMAB FOR DIABETIC MACULAR EDEMA REFRACTORY TO MULTIPLE PRIOR TREATMENTS.

Purpose: Diabetic macular edema can be refractory to multiple treatment modalities. Although there have been anecdotal reports of ranibizumab showing efficacy when other modalities provided limited benefit, little has been published on treatment for refractory diabetic macular edema. This study sought to investigate this observation further.

A 12-MONTH, SINGLE-MASKED, RANDOMIZED CONTROLLED STUDY OF EYES WITH PERSISTENT DIABETIC MACULAR EDEMA AFTER MULTIPLE ANTI-VEGF INJECTIONS TO ASSESS THE EFFICACY OF THE DEXAMETHASONE-DELAYED DELIVERY SYSTEM AS AN ADJUNCT TO BEVACIZUMAB COMPARED WITH CONTINUED BEVACIZUMAB MONOTHERAPY.

Purpose: To determine whether a dexamethasone intravitreal implant 0.7 mg (dexamethasone delivery system [DDS], Ozurdex) combined with bevacizumab 1.25 mg (Avastin) provides greater benefit than bevacizumab monotherapy in eyes with diabetic macular edema with incomplete response to multiple antivascular endothelial growth factor injections.

Influence of the Vitreomacular Interface on Treatment Outcomes in the Comparison of Age-Related Macular Degeneration Treatments Trials.

Objective: To assess the association of the vitreomacular interface with outcomes of eyes treated with anti-vascular endothelial growth factor drugs for neovascular age-related macular degeneration (AMD).

Design: Prospective cohort study within a multicenter, randomized clinical trial.

Participants: Patients enrolled in the Comparison of AMD Treatments Trials (CATT).

Ocular metastasis of colorectal cancer: An uncommon presentation of a common malignancy.

Approximately 20% of patients with colorectal cancer have metastatic disease at time of diagnosis, and another 25-35% develop metastases during the course of their disease. Liver, peritoneum, and lungs are the most common sites of metastases. We report the case of a 60-year-old female who presented with ocular metastasis 4 years after her initial curative-intent treatment for T3N1M0 rectal adenocarcinoma.

A 6-month, subject-masked, randomized controlled study to assess efficacy of dexamethasone as an adjunct to bevacizumab compared with bevacizumab alone in the treatment of patients with macular edema due to central or branch retinal vein occlusion.

Aims: To determine if intravitreal bevacizumab combined with the dexamethasone intravitreal implant 0.7 mg improves visual acuity and macular thickness more than bevacizumab monotherapy in eyes with macular edema due to branch and central retinal vein occlusions.

Methods: Thirty eyes were randomly assigned to receive either combination therapy or bevacizumab monotherapy.

Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema.

Purpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME).