Rho Kinase Inhibitors: Strategies in Glaucoma Treatment in Older Adults.

Glaucoma is a leading cause of irreversible blindness which preferentially affects older individuals. No medications or therapies which are currently in our arsenal actually treat glaucoma itself. We know that intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma. The primary treatments for glaucoma include medications, laser therapies, and surgical therapies. The Rho kinase inhibitors are the newest class of medications currently on the market and in development for topical IOP-lowering therapy. Studies have shown their ability to lower eye pressure individually and in combination with other medications. Their ability to potentially provide neuroprotective effects for disease modification also gives this class exciting potential for glaucoma treatment.

Outcome of combined trabeculectomy with cataract surgery in patients on prostaglandin analogs and aqueous suppressants.

PURPOSE: To compare the effect of prostaglandin analogs (PGA) against other glaucoma medications (non-PGA) on the intraocular pressure (IOP) outcomes of combined trabeculectomy with phacoemulsification, and the conjunctival cell profile in persons with primary open-angle (POAG) and pseudoexfoliation glaucoma (PXFG). METHODS: A prospective cohort study was conducted among 116 patients with POAG or PXFG on glaucoma medications for a minimum of 3 months undergoing glaucoma triple procedure. Patients were divided into two groups (PGA and non-PGA) based on preoperative exposure to PGA. IOP outcomes were assessed for up to 2 years. Conjunctival biopsy specimens were obtained at the time of surgery, and histopathological analysis was performed. RESULTS: Forty-two patients were in the PGA group, 67 were in the non-PGA group, and seven were lost to follow-up. The non-PGA group had lesser mean postoperative IOP and needed fewer postoperative medications compared to the PGA group in all visits up to 2 years. The non-PGA group had better complete success rate (50.7% vs. 14.3%, P < 0.001). Kaplan-Meier survival estimates showed a significant difference in cumulative complete success rate between non-PGA (67%) and PGA (26%) by 24 months ( P < 0.001). The Cox proportional model showed the type of drug to be significantly associated with surgical failure. Histopathological analysis revealed that the PGA group had higher numbers for each type of inflammatory cell (except mast cells) compared to the non-PGA group. CONCLUSION: Patients on PGA are likely to have a higher postoperative IOP and may need more medications for IOP control after a glaucoma triple procedure.

Reducing ophthalmic surgical waste through electronic instructions for use: a multisociety position paper.

Every ophthalmic surgical supply, including intraocular lenses (IOLs), IOL cartridges, and ophthalmic viscosurgical device syringes, is packaged with instructions for use (IFU). These pamphlets are printed in multiple languages and, in the case of an IOL, significantly increase the size and weight of the packaging. To eliminate this significant and unnecessary source of waste, we recommend that manufacturers move to Quick Response codes that link to online electronic IFU (e-IFU) as a sensible alternative. In addition to reducing carbon emissions and manufacturing costs, e-IFU can be updated more easily and accessed by surgeons in the clinic, where IOL models and powers are selected. Varying and inconsistent IFU requirements between different countries are a barrier to wider adoption of e-IFU by the ophthalmic surgical industry. Regulatory agencies in every country should allow and encourage e-IFU. This position paper has been endorsed by the 3 major societies that sponsor EyeSustain, a consortium of global societies dedicated to advancing sustainability in ophthalmology.

Comparison of Ophthalmologist and Large Language Model Chatbot Responses to Online Patient Eye Care Questions.

Importance: Large language models (LLMs) like ChatGPT appear capable of performing a variety of tasks, including answering patient eye care questions, but have not yet been evaluated in direct comparison with ophthalmologists. It remains unclear whether LLM-generated advice is accurate, appropriate, and safe for eye patients. Objective: To evaluate the quality of ophthalmology advice generated by an LLM chatbot in comparison with ophthalmologist-written advice. Design, Setting, and Participants: This cross-sectional study used deidentified data from an online medical forum, in which patient questions received responses written by American Academy of Ophthalmology (AAO)-affiliated ophthalmologists. A masked panel of 8 board-certified ophthalmologists were asked to distinguish between answers generated by the ChatGPT chatbot and human answers. Posts were dated between 2007 and 2016; data were accessed January 2023 and analysis was performed between March and May 2023. Main Outcomes and Measures: Identification of chatbot and human answers on a 4-point scale (likely or definitely artificial intelligence [AI] vs likely or definitely human) and evaluation of responses for presence of incorrect information, alignment with perceived consensus in the medical community, likelihood to cause harm, and extent of harm. Results: A total of 200 pairs of user questions and answers by AAO-affiliated ophthalmologists were evaluated. The mean (SD) accuracy for distinguishing between AI and human responses was 61.3% (9.7%). Of 800 evaluations of chatbot-written answers, 168 answers (21.0%) were marked as human-written, while 517 of 800 human-written answers (64.6%) were marked as AI-written. Compared with human answers, chatbot answers were more frequently rated as probably or definitely written by AI (prevalence ratio [PR], 1.72; 95% CI, 1.52-1.93). The likelihood of chatbot answers containing incorrect or inappropriate material was comparable with human answers (PR, 0.92; 95% CI, 0.77-1.10), and did not differ from human answers in terms of likelihood of harm (PR, 0.84; 95% CI, 0.67-1.07) nor extent of harm (PR, 0.99; 95% CI, 0.80-1.22). Conclusions and Relevance: In this cross-sectional study of human-written and AI-generated responses to 200 eye care questions from an online advice forum, a chatbot appeared capable of responding to long user-written eye health posts and largely generated appropriate responses that did not differ significantly from ophthalmologist-written responses in terms of incorrect information, likelihood of harm, extent of harm, or deviation from ophthalmologist community standards. Additional research is needed to assess patient attitudes toward LLM-augmented ophthalmologists vs fully autonomous AI content generation, to evaluate clarity and acceptability of LLM-generated answers from the patient perspective, to test the performance of LLMs in a greater variety of clinical contexts, and to determine an optimal manner of utilizing LLMs that is ethical and minimizes harm.

Validation of a portable, non-mydriatic fundus camera compared to gold standard dilated fundus examination using slit lamp biomicroscopy for assessing the optic disc for glaucoma.

PURPOSE: To evaluate the sensitivity and specificity of a portable non-mydriatic fundus camera to assess the optic disc for glaucoma. METHODS: We conducted a single-site, cross-sectional, observational, instrument validation study. Non-mydriatic fundus photographs centred at the optic disc were obtained from 276 eyes of 68 glaucoma and 70 normal patients, using a portable fundus camera (Smartscope, Optomed, Oulu, Finland). A senior Glaucoma consultant, masked to the patient's study participation, performed a gold standard dilated fundus examination to make the diagnosis of glaucoma. Following this, a mydriatic photograph was taken by a standard table-top fundus camera. All the images were digitalized and de-identified by an independent investigator and presented to two remote graders, masked to the patients, their diagnoses, and photographic modality. Based on individual disc characteristics, a diagnosis of screening positive or negative for glaucoma was made. In the end, the independent investigator re-identified the images. Sensitivity and specificity to detect glaucoma with the undilated Smartscope camera was calculated compared to dilated fundus examination. RESULTS: Grading remote images taken with the portable non-mydriatic fundus camera showed a sensitivity of 96.3% (95% confidence interval (CI): 91.6-98.8%) and 94.8% (95% CI: 89.7-97.9%) and a specificity of 98.5% (95% CI: 94.9-99.8%) and 97.8% (95% CI: 93.9-99.6%) for the two graders respectively as compared to gold standard dilated fundus examination. CONCLUSION: The non-mydriatic Smartscope fundus images have high sensitivity and specificity for diagnosing glaucoma remotely and thus may be an effective tool for use in community outreach programs.

Detection of Posterior Segment Eye Disease in Rural Eye Camps in South India: A Nonrandomized Cluster Trial.

PURPOSE: Rural screening camps in India historically have focused on detection of cataract and uncorrected refractive error. This study aimed to increase detection, referral, and follow-up for posterior segment diseases (PSDs) in rural eye camps using a novel technology-driven eye camp model. DESIGN: A clustered nonrandomized trial in the catchment area of Aravind Eye Care System (AECS) Pondicherry, to compare 2 eye camp models: the traditional AECS eye camp model and the novel, technology-driven, eye camp model. PARTICIPANTS: Patients 40 to 75 years of age who attended free camps conducted by AECS Pondicherry. Those with corneal pathologic features were excluded because this precluded an adequate view of the posterior segment to screen for PSD. METHODS: The clinical protocols in the 2 arms were standardized and the same study team was used in both study arms. The unit of allocation to the 2 study arms was at the level of the eye camp, rather than the level of the individual study participant. MAIN OUTCOME MEASURES: The primary study outcome was detection of suspected PSD (glaucoma, diabetic retinopathy, age-related macular degeneration, other PSDs). Secondary outcomes included: (1) the proportion of referred participants who underwent an examination at the base hospital and (2) the proportion with confirmed PSD on examination at the base hospital. RESULTS: The study included 11 traditional and 18 novel eye camps with a total of 3048 participants (50% in each study arm). The mean age of all participants was 58.4 ± 9.1 years and 1434 participants (47%) were men. The proportion receiving a referral for PSD was significantly greater in the novel (8.3%) compared with the traditional (3.6%) eye camp (P < 0.001; risk ratio, 2.31; 95% confidence interval, 2.30-2.34). Among the 183 participants referred from the camps for PSD, 73 (39.9%) followed up for further evaluation at the base hospital. CONCLUSIONS: In a resource-constrained setting, use of digital fundus photography in novel eye camps resulted in increased detection of and referral for PSD. Further research is needed to determine whether this intervention is cost effective and may contribute to prevention of avoidable blindness and visual impairment in South India. Further research also is needed to improve follow-up of patients referred from camps for suspicion of PSD.

The Aravind Pseudoexfoliation Study: 5-Year Postoperative Results. The Effect of Intraocular Lens Choice and Capsular Tension Rings.

PURPOSE: We compared rates of intraocular lens (IOL) decentration, neodymium-doped yttrium aluminum garnet capsulotomy for posterior capsule opacification (PCO), and visual acuity (VA) in eyes with and without pseudoexfoliation (PEX) 5 years after undergoing cataract surgery. DESIGN: Prospective comparative interventional study. METHODS: This multicenter study population included 1 eye of both 930 cataract patients with and 470 cataract patients without uncomplicated PEX (no small pupils or phacodonesis) all undergoing phacoemulsification by experienced Aravind Eye Care System surgeons. Eyes were randomized to either 1- or 3-piece intraocular lenses (IOLs). PEX eyes were also randomized to either receive or not receive a capsule tension ring. The main outcome measures included IOL decentration and PCO. Secondary outcomes included postoperative best-corrected VA. RESULTS: Follow-up was 86.2% in the PEX group and 86.7% in the control group at 5 years. The PEX group was older (P < .001) and had more men (P = .01). IOL decentration at 5 years was equally prevalent in PEX and control eyes (1.0% vs 1.1%, respectively, P = .8). Neodymium-doped yttrium aluminum garnet posterior capsulotomy rates for PCO were similar in the PEX group when compared with control subejcts (5.3% compared with 3.2%, respectively, P = .07). Best corrected VA was better at baseline and years 2 and 3 in the control group (P = .0001, P = .0005, and P = .02); however, there was no difference in BCVA at years 1, 4, and 5 between the PEX and control groups (P = .09, P = .29, and P = .5). CONCLUSION: In a large-scale, long-term, prospective comparative study of cataract surgery in eyes with uncomplicated PEX, the risks of IOL decentration and PCO were low and comparable to that in control subjects. When approaching cataract surgery in eyes with relatively uncomplicated PEX, neither IOL choice (1- vs 3-piece acrylic IOL) nor the presence/absence of a capsule tension ring affects outcomes at 5 years.

Rho-Associated Kinase Inhibitors: Evolving Strategies in Glaucoma Treatment.

Glaucoma, a group of progressive optic neuropathies with similar patterns of tissue loss, is primarily treated with medical therapy, followed by laser therapy and, later, incisional surgery. Aside from the introduction of prostaglandin analogs, topical carbonic anhydrase inhibitors, and topical alpha-agonists in the 1990s, no new pharmaceutical agents to lower intraocular pressure (IOP) have been introduced for approximately 20 years. The Rho kinase inhibitors represent a new class of glaucoma medications that inhibit the downstream pathway of the Rho family of small G-proteins to increase outflow from the conventional (trabecular) outflow pathway in the eye. Several of these Rho kinase inhibitors, ripasudil and netarsudil, have recently reached the market and are used in clinical practice in several countries. A fixed-dose combination of latanoprost and netarsudil was also very recently approved (2019) by the US FDA. Several other novel agents are undergoing clinical trials. These drugs are poised to act as adjuncts to already established medical therapy for further lowering of IOP in the treatment of glaucoma.

Cataract surgery and environmental sustainability: Waste and lifecycle assessment of phacoemulsification at a private healthcare facility.

PURPOSE: To measure the waste generation and lifecycle environmental emissions from cataract surgery via phacoemulsification in a recognized resource-efficient setting. SETTING: Two tertiary care centers of the Aravind Eye Care System in southern India. DESIGN: Observational case series. METHODS: Manual waste audits, purchasing data, and interviews with Aravind staff were used in a hybrid environmental lifecycle assessment framework to quantify the environmental emissions associated with cataract surgery. Kilograms of solid waste generated and midpoint emissions in a variety of impact categories (eg, kilograms of carbon dioxide equivalents). RESULTS: Aravind generates 250 grams of waste per phacoemulsification and nearly 6 kilograms of carbon dioxide-equivalents in greenhouse gases. This is approximately 5% of the United Kingdom's phaco carbon footprint with comparable outcomes. A majority of Aravind's lifecycle environmental emissions occur in the sterilization process of reusable instruments because their surgical system uses largely reusable instruments and materials. Electricity use in the operating room and the Central Sterile Services Department (CSSD) accounts for 10% to 25% of most environmental emissions. CONCLUSIONS: Surgical systems in most developed countries and, in particular their use of materials, are unsustainable. Results show that ophthalmologists and other medical specialists can reduce material use and emissions in medical procedures using the system described here.

New pharmacotherapy for the treatment of glaucoma.

INTRODUCTION: Glaucoma is the second leading cause of blindness in the world and current pharmacotherapies for glaucoma have remained relatively unchanged (with the exception of fixed combinations of previously available medications) since the mid-1990s with the development of prostaglandin analogues. Now, with both new formulations and new classes of medications with novel mechanisms of action, the medical therapy of glaucoma may be heralding a new dawn in medical management. Areas covered: This review outlines new topical therapies for intraocular pressure (IOP) lowering treatment, in addition to new formulations, preservative-free options, and advances in glaucoma medical therapy delivery. We performed a comprehensive search for published studies for glaucoma medical therapy using the electronic database PubMed. A manual search for each therapy or delivery system was also performed. Expert commentary: These advances in glaucoma therapy have the potential to overcome many barriers to glaucoma's medical care, particularly in terms of adherence. However, both time and research are needed to prove the relative efficacy and safety of these new pharmacotherapies and products, helping us decide their role in the treatment of elevated intraocular pressure. We are hopeful that these new developments in therapy may bring more options for glaucoma medical therapy.

Nonmedical Out-of-Pocket Patient and Companion Expenditures Associated With Glaucoma Care.

PURPOSE: Nonmedical out-of-pocket cost to both patients and their companions of office visits for routine glaucoma care has not been extensively studied in the United States. We evaluate potential key predictors of patient expenditures that are critical to assessing the cost-effectiveness of glaucoma health care delivery. MATERIALS AND METHODS: In total, 300 patients responded to the survey in 3 clinics in 2 clinical practice settings. Main outcome measures included both average visit and yearly expenditures. RESULTS: Of the 300 patients, the majority were female (n=187, 62.3%) and African American (n=171, 57.0%). The median age was 66 years. The median [range; mean (SD)] expenditure per patient visit was $22.10 ($11.1, $42.9; $44.1 (72.8)). Patients with companions paid $38.77 more in average visit expenditure (ß: 0.87, P<0.001). The average visit expenditure for retired patients was $17.37 less when compared with nonretired patients (ß: -0.4, P=0.004). Patients living in a rural or suburban area paid $43.91 and $14.13 more per visit, respectively (ß: 0.73, P=0.0004; ß: 0.31, P=0.03), compared with patients living in an urban area. Patients with noncommercial insurance paid $24.01 less in average visit expenditure (ß: -0.66, P=0.0008). The median yearly patient expenditure was $96.70 [$44.6, $222.7; $210.4 (333.9)]. Patients with companions paid $192.37 more in yearly expenditure (ß: 0.9, P<0.001) than those without companions, whereas retired patients paid $80.83 less in yearly expenditure (ß: -0.39, P=0.03) than nonretirees. Patients with noncommercial insurance paid $109.34 less in yearly expenditure (ß: -0.63, P=0.01). CONCLUSIONS: Although a small part of the total cost of glaucoma care, nonmedical out-of-pocket costs constitute a substantial noncovered medical expense to most patients in the United States. Patients who are employed, come with companions, live in nonurban areas, or are on Medicare have greater expenditures.

Microinvasive Glaucoma Surgery: An Evidence-Based Assessment.

INTRODUCTION: The advent of Microinvasive Glaucoma Surgery (MIGS) offers a novel approach in the treatment of glaucoma with the number of procedures developing at an exciting pace. AREAS COVERED: MIGS procedures aim to lower intraocular pressure (IOP) via four mechanisms: (1) increasing trabecular outflow, (2) increasing outflow via suprachoroidal shunts, (3) reducing aqueous production, and (4) subconjunctival filtration. A comprehensive search for published studies for each Microinvasive Glaucoma Surgery (MIGS) device or procedure was undertaken using the electronic database PubMed. Search terms included 'minimally invasive glaucoma surgery', 'microincisional glaucoma surgery', and 'microinvasive glaucoma surgery'. A manual search for each device or procedure was also performed. After review, randomized control trials and prospective studies were preferentially included. EXPERT OPINION: These procedures offer several benefits: an improved safety profile allowing for intervention in earlier stages of glaucoma, combination with cataract surgery, and decreased dependence on patient compliance with topical agents. Established MIGS procedures have proven efficacy and more recent devices and procedures show promising results. Despite this, further study is needed to assess the long term IOP-lowering effectiveness of these procedures. Particularly, rigorous study with more randomized control trials and head-to-head comparisons would allow for better informed clinical and surgical decision-making. MIGS offers new solutions for glaucoma treatment.

New classes of glaucoma medications.

PURPOSE OF REVIEW: To discuss recent advances in the medical management of glaucoma and to highlight future medical therapies currently in development. RECENT FINDINGS: In 1996, latanoprost (Xalatan) was approved in the United States as a new chemical entity and new class (prostaglandin analogs) for the topical treatment of ocular hypertension and glaucoma. In the period from the late 1990s-2010s, while there were additional new chemical entities, fixed dose combinations, and formulation improvements, there were no new classes of ocular hypotensive medications approved worldwide. We summarize new pharmacological treatments that are currently in clinical trials - new classes, new molecules and new delivery systems. SUMMARY: Although challenges in medical treatment of glaucoma exist, particularly in patient adherence, medical therapy remains the first line treatment for almost all glaucoma patients. Few new medications for glaucoma therapy are currently available for our patients, but multiple drugs with novel mechanisms of action, new formulations, and new delivery mechanisms are currently in development.