Clinical Outcomes of MicroPulse Transscleral Laser Therapy with the Revised P3 Delivery Device.

Aim: To evaluate the success and safety of MicroPulse transscleral laser therapy (TLT) on intraocular pressure (IOP) reduction in adults with uncontrolled glaucoma using different total treatment durations, sweep velocities, and a number of sweeps utilizing the revised MicroPulse P3 delivery device. Materials and methods: A single-center Institutional Review Board (IRB) approved multiple cohort studies of MicroPulse TLT with the revised MicroPulse P3 delivery device, which was conducted in 61 eyes from 40 adults with uncontrolled glaucoma. Eyes that received 50-second (GI, GII, and GIII) and 60-second (GIV, GV, and GVI) treatment applications between May and October 2020 were reviewed. Each hemisphere received a total of five, four, or three sweeps. The patient's IOP and glaucoma medications were monitored over 12 months follow-up. Qualified success was defined as an IOP of ≤21 mm Hg and/or reduction of ≥20% from baseline at 12 months, with no secondary glaucoma reinterventions. Complete success was defined as meeting the above criteria with no increase in glaucoma medications at 12 months. All eyes requiring a glaucoma surgical intervention were considered a failure. Results: Qualified success was achieved in 83.6% of eyes, while complete success was achieved in 75.4% of eyes. In eyes receiving 50-second applications of five, four, or three sweeps (GI, GII, and GIII), 70, 90, and 91% achieved qualified success, respectively; in eyes receiving 60-second applications of five, four, or three sweeps (GIV, GV, and GVI), 78, 82, and 90% achieved qualified success, respectively. Within each subgroup, mean IOP reductions ranged from 32.8 to 49.4% and were statistically significant (p < 0.008). The failure rate was 16.4%, and at least one eye failed in each subgroup. Conclusions: MicroPulse TLT with the revised MicroPulse P3 delivery device and relatively low total energy levels is safe and effective at lowering IOP. Efficacy appears to increase with longer treatment durations and slower sweep velocities, but statistical differences between age and clinical differences between baseline IOP measurements limit comparison between subgroups. Clinical significance: There is a lack of literature evaluating the safety and IOP-lowering success of the revised MicroPulse P3 delivery device using different total treatment durations, sweep velocities, and number of sweeps. How to cite this article: Checo LA, Dorairaj S, Wagner IV, et al. Clinical Outcomes of MicroPulse Transscleral Laser Therapy with the Revised P3 Delivery Device. J Curr Glaucoma Pract 2024;18(1):10-15.

Tracking Online Interest in Artificial Intelligence in Ophthalmology Using Google Trends.

PURPOSE: To examine trends in internet search queries related to artificial intelligence (AI) in ophthalmology and determine the correlation between online interest in AI, capital investment in AI, and peer-reviewed indexed publications regarding AI and ophthalmology. METHODS: Online search trends for "AI retina", "AI eye", and "AI healthcare" were obtained via Google Trends from 2016 to 2022 on a relative interest scale in 1-week intervals. Global venture financing of AI- and machine learning (ML)-focused companies in healthcare was tracked from 2010 to 2019 from the consulting company, Klynveld Peat Marwick Goerdeler (KPMG), and the technology market intelligence company, CB Insights. Citation count from pubmed.gov was determined using the search query "artificial intelligence retina" from 2012 to 2021. RESULTS: An increasingly linear growth in online search trends for "AI retina", "AI eye", and "AI healthcare" keyword searches was observed between 2016 and 2022. Global venture financing of AI and ML companies in healthcare also increased exponentially over the same time frame. There was an exponential increase in citations with nearly a 10-fold increase as reported by PubMed from 2015 onwards for the "artificial intelligence retina" search query. There was a significant and positive correlation between online search trends and investment trends (correlation coefficients of 0.98-0.99 and p-values <0.05) and between online search trends and citation count trends (correlation coefficients of 0.98-0.99 and p-values <0.05). CONCLUSIONS: These results demonstrate that the applications of AI and ML in ophthalmology are increasingly being investigated, financed, and formally researched, suggesting a prominent role for AI-derived tools in ophthalmology clinical practice in the near future.

OFFICE MANAGEMENT OF OZURDEX IMPLANT DISLOCATION INTO THE ANTERIOR CHAMBER.

PURPOSE: To describe a novel office procedure that permits the repositioning of an Ozurdex implant from the anterior chamber back into the vitreous cavity. METHODS: Description of an office technique for Ozurdex repositioning using a 30-gauge needle. RESULTS: In both cases, the Ozurdex implant was successfully returned to the vitreous cavity. In Case 1, the patient's visual acuities 1 and 2 weeks after this were 20/70 and 20/40, respectively, and had no further complications. In Case 2, the patient returned 1 week later, with the implant remaining posterior and a visual acuity of 20/40. CONCLUSION: The success of this novel technique in these cases demonstrates the potential to avoid a surgical procedure in the event of Ozurdex implant migration to the anterior chamber, while at the same time allowing the Ozurdex implant to remain effective in the eye.

Molecular Modeling and Phenotypic Description of a Patient with a Novel Exonic Deletion of GALNS with Resultant Morquio Syndrome with Two Successful Pregnancies.

In this report, we describe phenotypic features of a patient with mucopolysaccharidosis type IVA (Morquio syndrome) harboring a novel exon 1 deletion in GALNS with enzymatic confirmation consistent with Morquio syndrome. To our knowledge, this is the first reported case of this variant. Additionally, we protein modelled wild-type GALNS and the pathogenic variant with an exon 1 deletion for comparative analysis using statistical mechanics methods described herein. We demonstrate that, even when the protein is translated, the mutation would affect protein stability and function via homodimer interaction modifications. Lastly, given the patient's 2 successful pregnancies, data about the management of pregnancies in mucopolysaccharidoses are reviewed, and we discuss the management of pregnancy in patients with Morquio syndrome.

24-Month Outcomes of Ahmed ClearPath® Glaucoma Drainage Device for Refractory Glaucoma.

Purpose: To describe the safety and efficacy of the Ahmed ClearPath® (ACP) 250 mm2 glaucoma drainage device (GDD) in the treatment of refractory primary open-angle glaucoma (POAG). Patients and methods: This was a retrospective, noncomparative, single-surgeon, interventional case series of adult patients with medically ± surgically refractory POAG undergoing ACP implantation. Intraocular pressure (IOP), the number of glaucoma medications, and complications were recorded over 24 months of follow-up. Primary outcomes included mean reductions in both IOP and medication use through 24 months, and secondary outcomes included the proportion of eyes achieving an IOP between 6 and 19 mmHg, IOP reduction by ≥20%, and reduction by ≥1 medication at last mean follow-up. Results: Twelve eyes of 11 patients (mean age 71.3 ± 14.1 years) fit inclusion criteria and were enrolled. Most patients were Caucasian (n = 8), female (n = 10), and all had severe POAG (n = 11). The mean last follow-up was 18 months, at which time the mean (standard deviation) baseline IOP of 29.0 (7.6) mmHg was reduced to 12.2 (4.0) mmHg (58% reduction). 91.7% of eyes achieved an IOP between 6 and 19 mmHg, and 100% of eyes met an IOP reduction of ≥20%. Mean baseline number of glaucoma medications was 3.0 (0.9) and was reduced to 0.5 (0.7) at last mean follow-up (83.3% reduction), with 91.7% of eyes using ≥1 fewer medications. No long-term complications were observed, and short-term complications (mild hyphema, inflammation, and pain) were resolved by month 3. Conclusion: To our knowledge, this is the second long-term study evaluating the efficacy of the Ahmed ClearPath drainage device in adult patients, and the first study with 24-months follow-up. The ACP device is safe and effective at reducing both IOP and medication burdens in patients with severe POAG. Additionally, minimal short-term complications were noted with no long-term adverse effects, increasing comfort for both the surgeon and the patient.

There's Danger in the Drops: Systemic Effects of Ophthalmic Drops Used to Treat Glaucoma.

Glaucoma is a common eye disorder and an irreversible cause of blindness worldwide. There are several treatment options for this condition, with the traditional first-line treatment being ophthalmologic drops. Although administered topically, it is associated with inadvertent systemic absorption leading to a potential for both local and systemic side effects. We discuss the case of a 71-year-old male who presented with a complaint of recurring episodes of distressing sensations including lightheadedness, dyspnea, chest pressure, and faintness. His past medical history included congestive heart failure, hypertension, hyperlipidemia, Barrett's esophagus, and glaucoma. Upon a thorough review of the patient's medications, it was discovered that he had recently been started on timolol ophthalmic drops. The patient then noted that his symptoms had begun after he started using the eye drops. After we recommended that the patient hold the use of the eye drops, these episodes stopped. When prescribing topical ophthalmologic drops, providers must educate patients on common systemic side effects of such drugs.

Adhesion GPCR Latrophilin 3 regulates synaptic function of cone photoreceptors in a trans-synaptic manner.

Cone photoreceptors mediate daylight vision in vertebrates. Changes in neurotransmitter release at cone synapses encode visual information and is subject to precise control by negative feedback from enigmatic horizontal cells. However, the mechanisms that orchestrate this modulation are poorly understood due to a virtually unknown landscape of molecular players. Here, we report a molecular player operating selectively at cone synapses that modulates effects of horizontal cells on synaptic release. Using an unbiased proteomic screen, we identified an adhesion GPCR Latrophilin3 (LPHN3) in horizontal cell dendrites that engages in transsynaptic control of cones. We detected and characterized a prominent splice isoform of LPHN3 that excludes a element with inhibitory influence on transsynaptic interactions. A gain-of-function mouse model specifically routing LPHN3 splicing to this isoform but not knockout of LPHN3 diminished CaV1.4 calcium channel activity profoundly disrupted synaptic release by cones and resulted in synaptic transmission deficits. These findings offer molecular insight into horizontal cell modulation on cone synaptic function and more broadly demonstrate the importance of alternative splicing in adhesion GPCRs for their physiological function.

Screening for Diabetic Retinopathy with a Nonmydriatic Ultra-Wide-Field Retina Camera by Family Medicine Physicians.

PURPOSE: Diabetic retinopathy (DR) is the leading cause of blindness among working-aged adults aged 20 to 74 years. Despite professional association guidelines that recommend yearly screening for DR, only about 60% of Americans with diabetes mellitus (DM) receive annual examinations. The purpose of this 2-phase study was to determine the ability of family medicine (FM) physicians to accurately interpret retinal images of patients with DM. METHODS: Five FM physicians received a 1-hour lecture on DR by a retinal specialist after which the physicians were shown 30 ultrawide-field retina images and asked to determine whether the images contained signs of DR (phase 1). PATIENTS: Patients with DM who had not received an eye examination within the past year underwent nonmydriatic retinal photography in a FM clinic (phase 2). The 5 FM physicians were asked to evaluate the images for signs of DR and the images were simultaneously sent to a retinal specialist for independent interpretation. The diagnoses of the FM physicians and retina specialist were compared. Patients were informed of their results and were asked to complete a brief telephone survey regarding their experience with the screening process. RESULTS: Thirty retina images, 5 with DR and 25 without DR, were included in the postlecture assessment. Each of the 30 images was reviewed by all 5 FM physicians. Of the 5 images with DR, 3 were correctly diagnosed by all 5 FM physicians, 1 was correctly diagnosed by 4, and 1 was accurately diagnosed by 3. Overall accuracy for the 5 FM physicians was 100%, 100%, 100%, 97%, and 87%. Among the 34 patients included in phase 2, 3 (8%) were diagnosed with DR by the retinal specialist but 8 (24%) were diagnosed with DR by the FM physicians. Of the 3 patients with DR confirmed by the retinal specialist, only 1 was detected by the FM physicians (sensitivity, 33%; 95% CI, 1% to 91%). Of the 31 patients without DR as determined by the retinal specialist, 24 were accurately diagnosed by the FM physicians (specificity, 77%; 95% CI, 59% to 90%). The screening procedure was considered easy/efficient by 28 of 31 (90%) respondents. CONCLUSION: To improve early detection of DR new screening methods should be considered. FM physicians were able to accurately identify DR on postlecture images but were not as accurate when evaluating images taken from patients in the FM clinic. Patients found the screening process to be easy and efficient. This study was limited by the small sample size, particularly the limited number of DR cases. Future studies that include cases with a wide variation of DR severity are needed to determine the accuracy of FM physicians at detecting DR in a clinical setting.

Genomics combined with a protein informatics platform to assess a novel pathogenic variant c.1024 A>G (p.K342E) in OPA1 in a patient with autosomal dominant optic atrophy.

BACKGROUND: Autosomal Dominant Optic Atrophy (ADOA) is caused by mutations in the Optic Atrophy 1 Gene which disrupts the OPA1 protein. This disruption affects the normal function of the protein; impairs fusion of the mitochondrial inner membrane; and prevents normal OPA1 protein degradation. These events cause damage in retinal ganglion cells that could affect the patients with symptoms ranging from none to legally blind. MATERIALS AND METHODS: Our study identifies a missense variant mutation, c.1024 A > G (p.K342E), in OPA1 gene causing ADOA. Diagnosed clinically in three family members and the presence of this mutation was confirmed in two members by genetic testing. Pathogenic variants in OPA1 impact the secondary protein structure and function by causing non-conservative amino acid substitutions. We also modeled this mutation and compared it to the wild type using statistical mechanics. RESULTS AND CONCLUSIONS: The proband's pathogenic variant, c.1024 A > G (p.K342E), is located in the GTPase domain of OPA1 and causes changes in the protein structure by affecting the oligomerization pattern thus resulting in ADOA. Identifying the pathogenic potential of the missense mutations in the OPA1 gene using neoteric protein modeling techniques would help in the early detection of ADOA in patients who have family history of blindness. This action would help in providing early follow up, possible treatment in the future, and genetic counseling. Abbreviations: ADOA: Autosomal Dominant Optic Atrophy; CYCS: Caspase Activator Cytochrome C; OPA1: Optic Atrophy Gene 1; RGC: Retinal Ganglion Cells; VUS: Variant of Uncertain Significance.

Artificial intelligence and COVID-19: A multidisciplinary approach.

The COVID-19 pandemic is taking a colossal toll in human suffering and lives. A significant amount of new scientific research and data sharing is underway due to the pandemic which is still rapidly spreading. There is now a growing amount of coronavirus related datasets as well as published papers that must be leveraged along with artificial intelligence (AI) to fight this pandemic by driving news approaches to drug discovery, vaccine development, and public awareness. AI can be used to mine this avalanche of new data and papers to extract new insights by cross-referencing papers and searching for patterns that AI algorithms could help discover new possible treatments or help in vaccine development. Drug discovery is not a trivial task and AI technologies like deep learning can help accelerate this process by helping predict which existing drugs, or brand-new drug-like molecules could treat COVID-19. AI techniques can also help disseminate vital information across the globe and reduce the spread of false information about COVID-19. The positive power and potential of AI must be harnessed in the fight to slow the spread of COVID-19 in order to save lives and limit the economic havoc due to this horrific disease.

A Novel Treatment for Neurotrophic Corneal Ulcer Using Topical Cenegermin (OXERVATE™) Containing Recombinant Human Nerve Growth Factor.

Neurotrophic keratitis represents a complex degeneration of the cornea that can result in debilitating symptoms and serious sight-threatening complications. Patients with neurotrophic keratitis (NK) usually present with a history of corneal injury or past surgical intervention involving damage to the corneal nerves; as well as, chronic ocular surface disease. This nerve damage results in sensory loss and poor healing to the corneal tissues. This poor ability to heal results in the downward spiral of events that NK patients are subject to, which can include corneal surface breakdown, ulceration, melting, and total perforation. Treatments to attempt to support the cornea to heal and then protect it have recently advanced beyond traditional treatments and may include amniotic membrane application, autologous serum eye drops, biologic eye drops, and various other supportive treatments. Even aggressive combinations of these, and many other treatments, can leave NK patients still uncontrolled and progressing to end-stage disease that would require invasive intervention resulting in an even worse prognosis. This case report describes a patient who demonstrated all three stages of NK. Multiple interventions were initiated, including tarsorrhaphy, autologous serum eye drops, Prokera amniotic membrane, antibiotics, bandage contact lenses (BCL) therapy, and PKP. However, the patient experienced variable and transient improvement with relapse within a few weeks with recurrent and persistent epithelial erosion and stromal ulceration. A novel eye drop, cenegermin (OXERVATETM), an ophthalmic solution containing 20 µg/mL of a recombinant form of human nerve growth factor (NGF), was added to her treatment regimen allowing for successful management of NK and restoration of corneal integrity.

The Ocular Manifestations of COVID-19 Through Conjunctivitis.

There is growing evidence that the novel coronavirus (SARS-CoV-2) is capable of transmission through the eye. Research suggests that infection by SARS-CoV-2 can produce an inflammation of the conjunctiva, which leads to redness and itchiness of the eyes. Furthermore, viral particles have been detected in conjunctival secretions of SARS-CoV-2 patients who present with conjunctivitis and is likely another mode of transmission. A 53-year-old male presented with a complaint of left eye irritation and upper eyelid swelling for the past 24 hours. The right eye had mild irritation but no lid swelling. The left upper eyelid was erythematous, swollen and had crusting along the lashes. There were mild inflammation and injection of the conjunctiva. The initial diagnosis was blepharitis, and it was recommended that he continue with the warm compresses, and doxycycline 100 mg to use if the symptoms worsened or did not improve. The patient underwent SARS-CoV-2 PCR testing as a requirement for travel the next day and was found to be positive for the virus. Over the following days, he developed fatigue and rhinitis but clinically improved within six days of his initial presentation. Physicians and health care workers should be aware of the ocular manifestations of SARS-CoV-2 to make a timely diagnosis of infected individuals. While requirements vary across institutions, it is highly recommended that healthcare workers consistently wear appropriate eye protection when interacting with patients to reduce the spread of disease and potential impact on ocular health from SARS-CoV-2. Additionally, to prevent ocular transmission, all healthcare workers should be immediately educated on the importance of eye protection.