Abstract: Macular neovascularization (MNV) is the hallmark of neovascular age-related macular degeneration (nAMD), one of the leading causes of vision loss in the developed world. The current MNV standard of care including frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections, although has revolutionized favorably the treatment, places a substantial burden on patients, caregivers, and physicians. Brolucizumab is a newly developed single-chain antibody fragment that inhibits activation of VEGF receptor 2 with in vitro affinity and potency comparable to commercially-available anti-VEGF agents. Its small molecular weight and its design allow for high solubility and retinal tissue penetration, and improve bynding affinity to the target. Also a high clearance rate leading to minimal systemic exposure was observed. Brolucizumab has shown similar gains in visual acuity compared with other anti-VEGF molecules but a higher and earlier resolution of nAMD related fluid, achieving sustained macular dryness with longer mantainance injection interval ranging from 8 to 12 weeks after monthly loading doses. Rare cases of ocular inflammation also including retinal vasculitis and retinal vascular occlusions referred to an immune-mediated reaction posed safety concerns on selected patients and mantainance treatment interval shorter than 8 weeks.The present review summarizes several key points including the molecular structure and pharmacokinetics, the preclinical and clinical evidence of brolucizumab administration evaluating its efficacy, tolerability, and safety, extended dosing regimens and other indications still under clinical investigation.
Abstract: The rare disease of chronic infantile neurological cutaneous and articular (CINCA) syndrome, is caused by the over-secretion of interleukin (IL)-1β due to a gain-of-function NLRP3 gene mutation in the autosomal chromosome which often involves in eyes. In this report, we studied a 9-year-old girl with CINCA. The eyes were also involved and presented bilateral papilledema. Genetic testing revealed that the symptoms were caused by a novel gene mutation site (c.913G>A, p. D305N) in conservative domain exon-3 of NLRP3 which is gain-function gene of CINCA. The patient had the characteristic facial features, frontal fossa and saddle nose, manifested the generalized urticaria-like skin rash at two weeks after birth, periodic fever 6 months after birth, sensorineural deafness at 7 years old, and bilateral papilledema, aseptic meningitis and knee arthropathy at 9 years old. White cell counts, C-reactive protein increased and intracranial pressure raised to 300 mmH2O. The meningeal thickening enhanced by gadolinium in magnetic resonance imaging (MRI). Based on clinical features and genetic test, the girl was diagnosed bilateral papilledema secondary to CINCA and administered prednisone and lowered intracranial pressure medicine to resolve symptoms. With 3-year follow-up, patient had no inflammatory flare-up with visual acuity improvement. The finding of novel genetic mutation site (p. D305N) in NLRP3 gene expanded genotype spectrum associated with CINCA. This case also expanded the cause spectrum of papilledema and it highlighted systemic disease history for patients with bilateral papilledema.
Conjunctival flaps have previously proven to be effective in preserving the globe for individuals with severe ocular surface disease. Infectious keratitis, neurotrophic keratitis, nontraumatic corneal melts, descemetoceles, perforations, and corneal burns are all indications for this procedure. The flaps promote nutrition, metabolism, structure, and vascularity, as well as reduce pain, irritation, inflammation, and infection. Furthermore, patients avoid the emotional and psychological repercussions of enucleation or evisceration, while requiring fewer postoperative medications and office visits. Currently, fewer flaps are performed due to the emergence of additional therapeutic techniques, such as serum tears, bandage lenses, corneal grafting, Oxervate, amniotic membrane, and umbilical cord grafting. However, despite newer conservative medical methods, conjunctival flaps have been demonstrated to be useful and advantageous. Moreover, future technologies and approaches for globe preservation and sight restoration after prior conjunctival flaps are anticipated. Herein, we review the history, advantages, and disadvantages of various surgical techniques: Gundersen’s bipedicle flap, partial limbal advancement flap, selective pedunculated conjunctival flap with or without Tenon’s capsule, and Mekonnen’s modified inferior palpebral-bulbar conjunctival flap. The surgical pearls and recommendations offered by the innovators are also reviewed, including restrictions and potential complications. Procedures for visual rehabilitation in selective cases after conjunctival flap are reviewed as well.
