Emerging Oral Pharmaceuticals for Dry Age-Related Macular Degeneration: Mechanism of Action, Current Clinical Status, and Future Directions.

Dry age-related macular degeneration (AMD) has been historically managed with lifestyle modifications, monitoring for conversion to wet AMD, and vitamins. Recently there has been a flurry of research focused on discovering new targets to prevent worsening of dry AMD. In 2023, the US Food and Drug Administration approved the first two intravitreal complement inhibitors to slow the rate of geographic atrophy progression. However, serial intravitreal injections for a chronic progressive disease are burdensome for patients and have procedural risks. Therefore, there is significant research to discover novel oral medications to manage dry AMD. Several oral medications are currently in phase 2 and 3 clinical trials for dry AMD, whereas others have had recent readouts on their clinical trials and efficacy. The purpose of this review is to describe the therapeutic pathways currently being investigated and to provide an update on the clinical status of novel oral medications for the management of dry AMD. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

In-Office Vitreous Biopsy With a Vitreous Cutter and Manual Actuation.

In-office vitreous biopsy is currently performed with a 25-gauge needle or less frequently with a specialized in-office surgical system. This article demonstrates in-office vitreous biopsy with a standard vitreous cutter, using syringes to actuate the cutter. A 79-year-old woman presented six days after intravitreal bevacizumab with endophthalmitis. After subconjunctival anesthesia, a valved 27-gauge trocar was inserted through the pars plana. Two syringes were connected to a pneumatic 27-gauge Alcon vitrectomy handpiece and manually actuated by an assistant while the physician aspirated with a third syringe to obtain the vitreous biopsy. Intravitreal vancomycin and ceftazidime were injected. A total of 0.5 cc of fluid was collected without complications. Manual actuated vitrectomy reliably collects sufficient vitreous samples for diagnostic evaluation and may be safer and more effective than needle biopsy. [Ophthalmic Surg Lasers Imaging Retina 2024;55:116-118.].

Biomimetic Accommodating Intraocular Lens Using a Valved Deformable Liquid Balloon.

OBJECTIVE: Presbyopia is a common age-related condition that prevents people from focusing on near objects. The etiology of presbyopia continues to be debated, but the end effect of all postulated mechanisms is the lack of deformation of the human lens. Using our understanding of the biomechanical properties of the natural human lens, we created a unique accommodating intraocular lens. Although this lens can be used for lenticular disease such as myopia and hyperoperopia, this study addresses the needs of cataract patients with presbyopia. METHODS: The lens was implanted into presbyopic human cadaver eyes. Focal length of the lens was measured with simulated muscle contraction. Lens dimensions were measured using artificial tissue and a finite-element analysis (FEA) to simulate accommodation. Lens power was measured at various fill volumes. Accelerated soak testing for an equivalent of 7.4 years was performed and lens weight and optical transmittance were measured. RESULTS: Previously presbyopic human eyes were able to accommodate between 2.0 and 7.4 diopters after lens implantation. FEA and lens measurements demonstrated a change in curvature of the anterior and posterior portions of the lens during accommodation. After accelerated aging, lens weight remained unchanged and optical transmission was 96%. Lens power increased with fill volume. CONCLUSION: A deformable liquid lens reversed presbyopia, can be individualized by optically adjusting for each patient, is stable for long periods of time, and is compatible with minimally invasive surgical techniques. SIGNIFICANCE: A deformable liquid-filled lens can significantly improve accommodation over the presbyopic natural lens.

Performance analysis of new-generation vitreous cutters.

BACKGROUND: Despite their clinical advantages, smaller-diameter vitrectomy systems pose significant challenges in vitreous removal. The percentage of time the vitreous cutter port is open while cutting (duty cycle) is one of the primary factors that affect flow. Herein, we examine the effect of duty cycle on the flow performance of new-generation cutters relative to current instrumentation. METHODS: Performance of 25-gauge (ga) and 20-ga new-generation spring-return pneumatic cutters (n = 24 and n = 28 respectively) was analyzed relative to current-generation cutters, across their specified cut-speed range under clinical vacuum pressures of 500 mmHg (25-ga) and 200 mmHg (20-ga). A precision balance measured mass of water or porcine vitreous removed from a vial by a cutter; this was recorded in real-time and converted to flow rates. Frame-by-frame analysis of high-speed video was used to determine duty cycle. Data was analyzed using linear regression and the t-test. RESULTS: Compared with the current-generation, the new-generation cutters exhibit increasingly greater water flow rates at higher cut speeds (P < 0.001). Vitreous flow rates of the new-generation cutters are relatively constant as cut speed increases, and are significantly greater than those of the current-generation cutters at cut speeds of 1500 cuts per minute (CPM) or higher (P < 0.001). The new-generation 25-ga cutter exhibits greater vitreous flow rates at higher cut speeds than the current-generation 20-ga cutter: at 2000 and 2500 CPM, the new 25-ga cutter has 1.45 and 11.88 times the vitreous flow rate of the current 20-ga cutter (P < 0.001) respectively. Duty cycles of the new-generation cutters are significantly higher than those of the current-generation at all cut speeds (P < 0.001). CONCLUSIONS: Although a number of factors influence flow, the high and relatively constant vitreous flow rates of the new-generation cutters are most likely due to their maintenance of high duty cycle as cut speed increases. The findings illustrate that in optimizing duty cycle, the vitreous flow efficiency of smaller-diameter cutters can match or exceed that of larger diameter cutters.

Effect of mycorrhization on the accumulation of rishitin and solavetivone in potato plantlets challenged with Rhizoctonia solani.

The effect of colonization with the vesicular-arbuscular mycorrhizal fungus Glomus etunicatum on the content of rishitin and solavetivone was determined in potato plants cv. Goldrush challenged with Rhizoctonia solani. Mycorrhization stimulated significantly the accumulation of both phytoalexins in roots of plantlets challenged with R. solani but did not influence phytoalexin levels in non-challenged plantlet roots. No accumulation of solavetivone or rishitin was detected in shoots. In Petri dish bioassays, rishitin and solavetivone inhibited mycelial growth of R. solani.

Systemic and Local Responses Associated with UV- and Pathogen-Induced Resistance to Botrytis cinerea in Stored Carrot.

ABSTRACT The induction of resistance to Botrytis cinerea in carrot roots by UV radiation, a possible means for controlling storage diseases, was compared with systemic resistance induced by inoculation with the pathogen. UV radiation did not have any systemic effect, and disease resistance was induced only in tissues directly exposed to the radiation. Although UV radiation induced a local accumulation of 6-methoxymellein (6-MM), inoculation with B. cinerea caused 6-MM to accumulate systemically, away from the inoculation site. Because of amounts near or higher than the ED(50) (50% effective dose) for inhibiting B. cinerea found in both UV-treated and preinoculated roots at the time of challenge, 6-MM could be involved in both types of resistance. Freshly harvested carrots had a number of constitutive chitinases and beta-1,3-glucanases, which were not affected by UV radiation or inoculation. When challenged with B. cinerea, the induction of a 24-kDa chitinase was enhanced in UV-treated and preinoculated roots. Again, UV radiation had only a local effect in priming this chitinase response. Although UV- and pathogen-induced resistance in carrot may involve the same defenses, the responses are probably mediated differently, because UV radiation has an essentially local effect.