Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA disorder, presenting typically as a sequential, painless, subacute, optic neuropathy in young males. Despite the very limited therapeutic options in LHON, recent developments involving novel pharmacological agents and emerging gene therapy interventions have shown promising results for improved visual outcomes. A synthetic analogue of coenzyme Q (idebenone) is the most common medical treatment in LHON. In a multicentre, double-blind randomized, placebo-controlled clinical trial (Rescue of Hereditary Optic Disease Outpatient Study [RHODOS]), a dose of 900 mg/day of idebenone for 24 weeks was found to be well tolerated and safe. In a follow-up study (RHODOS-OFU), the visual acuity of 70% of patients enrolled in RHODOS was reassessed 30 months after discontinuation of idebenone. Results from this study suggested that visual acuity continued to improve even after discontinuation of the drug. Gene therapy has recently emerged as a potential treatment for LHON. RESCUE and REVERSE were two phase III clinical trials of viral-mediated gene therapy using lenadogene nolparvovec intravitreal injections in patients with early-stage LHON. Results in these trials have shown long-term safety and bilateral visual acuity improvement after unilateral intravitreal injections at 96 weeks, and sustained visual improvement after 3 years of treatment. The most recent phase III clinical trial in LHON (REFLECT) has shown significant improvement of vision after bilateral intravitreal injections of lenadogene nolparvovec compared with unilateral injections. These promising results suggest that, in the near future, LHON might become the first mitochondrial disorder to benefit from gene therapy.
Neurotrophic keratitis is a complex condition with a variety of aetiologies involving damage to the sensory nerves that innervate the cornea, resulting in potentially devastating ocular surface disease. Aetiologies include diabetes, prior herpesvirus keratitis, stroke or compressive damage to the trigeminal nerve, chronic ocular surface disease or contact lens overuse, among others. Management is multidisciplinary; of course, the underlying condition must be addressed and treated. The ocular surface must be stabilized, and depending on the severity, treatment options include artificial tears and lubrication, protective barriers (scleral lens, tarsorrhaphy), and growth factors that promote healing (serum tears, amniotic membrane). Finally, treatment can target restoration of corneal sensory innervation (cenegermin, corneal neurotization). Early recognition and treatment are important factors in reducing vision loss and long-term complications from neurotrophic keratitis.
Suprachoroidal injection is a unique, minimally invasive procedure for drug delivery to the posterior segment of the eye. Drugs can be delivered easily via microneedles that are slightly longer than the scleral and conjunctival thickness at pars plana. Suprachoroidal delivery of corticosteroids allows higher steroid concentration in the posterior segment tissues with minimal drug concentration in the anterior segment, which decreases the risk of other adverse ocular events like steroid-induced elevation of intraocular pressure and cataract progression. Several clinical trials have evaluated the safety and efficacy of suprachoroidal injection of triamcinolone acetonide in various ocular conditions. This article reviews the novel treatment as a promising route for drug delivery.
The introduction of vascular endothelial growth factor inhibitors has led to significant improvements for patients with neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO). Landmark trials – such as ANCHOR, MARINA and VIEW for nAMD and RIDE/RISE, VIVID and VISTA for DMO – showed positive results, including clinically meaningful gains in Early Treatment Diabetic Retinopathy Study letters, with anti-vascular endothelial growth factor agents now the standard of care for nAMD and DMO. More recent studies, including those investigating high-dose aflibercept in nAMD and DMO, have focused on durability of response by studying increased treatment intervals to reduce the treatment burden on patients and physicians alike. The PULSAR (nAMD) and PHOTON (DMO) trials included high-dose (8 mg) aflibercept at either 12-week or 16-week dosing intervals and showed non-inferior visual gains compared with the standard dose of 2 mg, with ≥83% of patients maintaining their extended dosing interval throughout the 48-week studies. This is certainly an exciting development, and it will be interesting to see how extended treatment durability will impact management paradigms for patients with nAMD and DMO.
Introduction: This article reports two cases of submacular choroidal granuloma from sarcoidosis, highlighting the critical importance of timely diagnosis and treatment for both visual and systemic prognosis. Case studies: Case 1 is a 60-year-old man who presented with blurred vision from a submacular choroidal granuloma. Initially, the lesion responded to oral prednisone, however, there was progression once the prednisone was stopped. One year later, he developed complete heart block and was diagnosed with cardiac sarcoidosis. He underwent pacemaker implantation and has been maintained on mycophenolate. Case 2 is a 35-year-old man who presented with distortion from a submacular choroidal granuloma that similarly responded to oral prednisone but progressed after it was discontinued. He had a chest computerized tomography scan and a subsequent lymph node biopsy that confirmed the diagnosis of sarcoidosis. He has remained stable and healthy, with 20/20 vision on methotrexate. Conclusion: Submacular choroidal granuloma from sarcoidosis is a rare condition that can cause vision loss if not treated promptly. These lesions usually respond to local or systemic corticosteroids. Diagnosis of these lesions is critical not only for visual preservation but also to prevent systemic complications.
