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Tertiary syphilis, which can develop years to decades after the initial infection, is characterized by chronic inflammatory damage affecting multiple organ systems.

A case of retinal detachment in tertiary syphilis

Videos

In celebration of Ophthalmology Times 50th anniversary, we asked leading experts in the field what they see as the biggest innovation in ophthalmology in the last 5 decades.

Part 4: Biggest innovations in ophthalmology in 50 years

Recent estimates show that there are over 2 billion users on Instagram, of which over 726.8 million interact with reels on the platform. 

Doctors warn TikTok & Instagram reels may be damaging eyes long-term

Uveal melanoma, which primarily affects Caucasian patients, is the most common primary intraocular tumor in adults2 that most often affects the choroid (90%), ciliary body (6%), and iris (4%)

Novel radiosurgical platform to treat a case of uveal melanoma

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Based on a physician's knowledge of the risk of non-payment, Medicare's Advance Beneficiary Notice should be used when the physician believes the service is unlikely to be covered since it may not be medically necessary or reasonable. The ABN explains to the patient that even though Medicare does not pay for a certain item or service does not mean that the patient shouldn't have it. The –GA modifier should be used on the ABN. If –GA is not appended, the patient will be informed in the Explanation of Benefits that they are not responsible for payment.

Advance Beneficiary Notice shifts responsibility for payment

A new therapeutic approach that combines eyelid pressure patching with the application of decellularized, dehydrated pure amniotic membrane basement membrane (AMBM), a type of amniotic membrane tissue (AMT), was highly successful and safe for healing persistent corneal epithelial defects,

 according to Kyle Linsey, MD, who is from the Cornea Service, Clearwater Eye and Laser Center, Clearwater, FL, and HCA Florida Bayonet Point Hospital, University of South Florida, Tampa.

Managing persistent corneal epithelial defects can be tricky, and, according to Linsey, typically consists of treatments such as frequent lubrication, immunomodulators, steroids, autologous serum or platelet-rich plasma tears, bandage contact lens, punctal occlusion, and in more advanced disease, pressure patching, epithelial debridement, scleral contact lenses, cenegermin, and AMT.

AMT offers a number of advantages to patients that includes rapid re-epithelialization of the persistent corneal epithelial defects in cases refractory to treatment,

 by addressing the ocular surface inflammation,

 at rates of re-epithelialization of 45.5% to 74.7%, independent of ulcer etiology.

 The treatment does not transfer viable stem cells

 but “supports damaged tissue, protects and shields defects from further degeneration or breakdown from external factors and promotes re-cellularization,

In addition, AMT stimulates proliferation and migration of limbal stem cells, suppresses neo-angiogenesis, inflammation, and scarring, contributes to AMT’s ability to support the healing of ocular surface disease

 and physically acts as a substrate for epithelial cell growth.

Multilayer AMT has been proposed for treating deep neurotrophic corneal ulcers

 and is more effective than autologous serum at healing corneal ulcers resulting from herpetic neurotrophic keratitis.

In his retrospective study, Linsey analyzed 144 eyes treated with either a single-layer or three-layer decellularized AMBA (Biovance 3L Ocular; Verséa Ophthalmics, Inc.) combined with a 24-hour eyelid pressure patch; 90% were treated with a single layer of AMBM and 10% with three layers of AMBM.

In the single-layer group, Linsey reported, all cases healed completely and the AMBM dissolved. In the three-layer group, all cases had improvements in the corneal staining; however, the AMBM did not dissolve in 20% to 30% of cases. No patients reported pain, discomfort, or infection.

This study found that combining eyelid pressure patching with AMT is a safe and effective approach for healing persistent corneal epithelial defects.

“AMT promotes epithelial cell proliferation, reduces inflammation and neuropathic pain, and limits scar formation.

 AMT can act as a mechanical barrier to protect the ocular surface, prevent evaporation and dryness, and maintain a stable tear film while serving as a scaffold for donor–recipient cell migration and integration.

 The integration of an eyelid pressure patch with dehydrated, decellularized AMBM treatment for advanced ocular surface disease leads to accelerated corneal healing and increased patient comfort,” Linsey concluded.

Linsey K. Use of an eyelid pressure patch concomitantly with a decellularized dehydrated amniotic membrane for ocular surface disease management. 

https://doi.org/10.1007/s40123-025-01094-2

Katzman LR, Jeng BH. Management strategies for persistent epithelial defects of the cornea. 

Ljubimov AV, Saghizadeh M. Progress in corneal wound healing. 

Rodríguez Calvo-de-Mora M, Domínguez-Ruiz C, Barrero-Sojo F, et al. Autologous versus allogeneic versus umbilical cord sera for the treatment of severe dry eye disease: a double-blind randomized clinical trial. 

Sánchez-González JM, Alonso-Aliste F, Borroni D, et al. Plasma rich in growth factors (PRGF) in transepithelial photorefractive keratectomy (TPRK). 

Fernandes M, Sridhar MS, Sangwan VS, et al. Amniotic membrane transplantation for ocular surface reconstruction. 

Prabhasawat P, Tesavibul N, Komolsuradej W. Single and multilayer amniotic membrane transplantation for persistent corneal epithelial defect with and without stromal thinning and perforation. 

Letko E, Stechschulte SU, Kenyon KR, et al. Amniotic membrane inlay and overlay grafting for corneal epithelial defects and stromal ulcers. 

Sheha H, Liang L, Li J, Tseng SC. Sutureless amniotic membrane transplantation for severe bacterial keratitis. 

Sheha H, Tighe S, Cheng AM, Tseng SC. A stepping stone in treating dendritic keratitis. 

Sell S, de la Presa M, Thakur S, Eslani M, Jeffrey J, Sheppard JD, Holland EJ, Cheung AY. Comparison of persistent epithelial defect treatment with sutureless cryopreserved and dehydrated amniotic membrane. 

Lacorzana J, Campos A, Brocal-Sánchez M, et al. Visual acuity and number of amniotic membrane layers as indicators of efficacy in amniotic membrane transplantation for corneal ulcers: a multicenter study. 

Füst A, Pállinger E, Stündl A, et al. Both freshly prepared and frozen-stored amniotic membrane cells express the complement inhibitor CD59. 

Walkden A. Amniotic membrane transplantation in ophthalmology: an updated perspective. 

Pogozhykh O, Hofmann N, Gryshkov O, et al. Repeated freezing procedures preserve structural and functional properties of amniotic membrane for application in ophthalmology. 

Dua HS. Amniotic membrane transplantation. 

Burman S, Tejwani S, Vemuganti GK, et al. Ophthalmic applications of preserved human amniotic membrane: a review of current indications. 

Thiex NW, Chames MC, Loch-Caruso RK. Tissue-specific cytokine release from human extra-placental membranes stimulated by lipopolysaccharide in a two-compartment tissue culture system. 

Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. 

Turkoglu E, Celik E, Alagoz G. A comparison of the efficacy of autologous serum eye drops with amniotic membrane transplantation in neurotrophic keratitis. 

Tighe S, Mead OG, Lee A, Tseng SCG. Basic science review of birth tissue uses in ophthalmology. 

A novel therapeutic strategy combining eyelid pressure patching with amniotic membrane tissue (AMT) has proven effective and safe for treating persistent corneal epithelial defects. Traditional management of these defects includes various treatments, but AMT offers advantages such as rapid re-epithelialization, inflammation reduction, and support for healing. A retrospective study of 144 eyes showed complete healing with single-layer AMT and improvement with three-layer AMT, with no reported pain or infection. This approach enhances corneal healing, reduces inflammation, and increases patient comfort, making it a promising option for ocular surface disease management.

Amniotic membrane tissue offers a number of advantages to patients.

Gaining control of persistent corneal epithelial defects using AMT and a pressure patch

Sadun discusses research targeting LHON

, Alfredo A. Sadun, MD, PhD, chief at Doheny Eye Center – UCLA, discusses a paper titled Coenzyme Q10 trapping in mitochondrial complex I underlies Leber's hereditary optic neuropathy.

The paper has been nominated for a Cozzarelli Prize, which is awarded annually to 6 research teams whose PNAS articles have made outstanding contributions to their field. Each team represents one of the 6 classes of the National Academy of Sciences (NAS): Physical and Mathematical Sciences; Biological Sciences; Engineering and Applied Sciences; Biomedical Sciences; Behavioral and Social Sciences; and Applied Biological, Agricultural, and Environmental Sciences.

“Yes, we were very proud of that paper,” Sadun said. “It came out in the Journal of the National Academy of Sciences a couple of months ago.”

Sadun is the senior author on the article.

“I’ve spent my life studying Leber's hereditary optic neuropathy, or LHON,” he explained in the conversation.“And it got into some really deep biology and then physics and then quantum mechanics as part of the answer. It's really neat to do something so fundamental and basic with implications that probably go beyond this disease, and go to how the chemistry of life works.”

Scientists at Doheny Eye Institute, in a collaboration with colleagues at UCLA and the University of Texas, have shown how a single gene mutation in the enzyme complex that produces the energy used by cells causes LHON.

According to a Doheny Eye Institute news release, the researchers found the mutation affects the cells’ tiny mitochondria, miniature power stations that generate the energy molecules called ATP, that all cells of the body require to do their jobs and stay alive. The mystery of how LHON causes blindness is now illuminated: the mutation causes alterations in quantum electron tunneling.

Quantum tunneling is an amazing process, totally unlike classical chemistry, that enables elementary particles, like electrons, to penetrate through energy barriers. What is now shown is that quantum tunneling is likely central to many biological reactions and may be key in explaining other human diseases.

Sadun worked with biophysicist Steven Barnes, PhD, both of Doheny Eye Institute and UCLA’s Department of Ophthalmology, tapped the expertise of UCLA Department of Chemistry’s Anastassia Alexandrova, PhD, and Jack Fuller, PhD, to address the disease using state-of-the-art computational chemistry tools.

Sadun pointed out that one mystery of the disease is why it strikes primarily young men in their 20s.

“The patient usually diagnosed with the disease is usually a health young person in his early 20s and thought everything was fine. It is a mysterious disease in many ways,” he told

. “There is no effective treatment in the United States. There is no FDA-approved treatment.”

Sadun noted that Idebenone has been approved by the European Medicines Agency for use in LHON.

According to scientists, the maternally-inherited genetic disorder typically waits for two decades before it strikes its victims, causing severe loss of vision or blindness, usually in young adult men, and to a lesser extent women, in their twenties.

According to the news release, the scientists previously showed that this disease kills the eye’s retinal ganglion cells (RGCs) not by causing poor energy production, but rather by producing ‘reactive oxygen species,’ or ROS, normal cellular molecules that when over-produced seriously impair cell protein function. In LHON, these damaging ROS are an unnoticed problem that waits decades before damage suddenly exceeds a threshold, triggering the death of RGCs, neurons that transmit electrical signals coding patterns of light from the eye to the brain.

In order to determine the origin of the ROS, the team of scientists looked at how the single genetic mutation affects a key subsection of the cell’s mitochondria with a single amino acid swap. It is in this subsection, called Complex I, that the mobility of the energy-trafficking molecule CoQ10 is seriously impaired. CoQ10, getting into and out of a tight-fitting channel in Complex I, defines the rate of the quantum tunneling of electrons that play a central role for generating ATP.

Powerful Molecular Dynamics simulations were performed using the National Supercomputer network to analyze the impact of the single amino acid swap from alanine to threonine in Complex I on the mobility of CoQ10 at different speeds via calculation of the positions and free energy of the molecules. They found that CoQ10 exits the mutated channel a billion times slower than it would in a normal channel.

The continuous supply of electrons to Complex I, now having nowhere to go, produces excessive rates of electron backup and spillage that generate ROS. This conclusion supports earlier observations that neurons with models of LHON produce near-normal amounts of ATP but high levels of ROS, which facilitate RGC death.

“We used molecular dynamics and FEP simulations to elucidate the mechanistic impact of the m.3460G>A mutation on the function of the ND1 protein, leading to Leber’s hereditary optic neuropathy,” the researchers concluded. “These simulations show how, in the case of the m.3460G>A mutation, the alanine to threonine substitution at position 52 leads to the extended CH3 and an additional OH in the path of the CoQ10. “

According to the study, this creates a kinetic hindrance for CoQ10 to pass through the binding channel. The scientists noted the thermal energy required to move the CoQ10 out of the channel is estimated about 50 kT, far too much to allow diffusion to occur at appreciable rates.

“Failed electron transfer will lead to electron spillage and ROS production at the proximal end of the FeS cluster series,” the scientists concluded. “ROS are a known cause of the blindness from Leber’s hereditary optic neuropathy, and this work thus links the molecular origin of ROS overproduction to the disease process.”

Fuller JT 3rd, Barnes S, Sadun LA, Ajmera P, Alexandrova AN, Sadun AA. Coenzyme Q10 trapping in mitochondrial complex I underlies Leber's hereditary optic neuropathy. Proc Natl Acad Sci U S A. 2023 Sep 26;120(39):e2304884120. doi: 10.1073/pnas.2304884120. Epub 2023 Sep 21. PMID: 37733737; PMCID: PMC10523484.

Scientists at the Doheny Eye Institute, in collaboration with UCLA chemists, demonstrate how a single gene mutation in an enzyme complex known to produce the energy required by cells causes a sudden, blinding disease.

Alfredo A. Sadun, MD, PhD, discusses research targeting LHON

A recurring feature at the 2024 American Society of Cataract and Refractive Surgery (ASCRS) Annual Meeting in Boston, Massachusetts, was the call for environmentally friendly practices worldwide, with the goal of decreasing the impact of ophthalmic surgeries on the planet.

A driving force in this movement is EyeSustain

 an organization dedicated to the development of such friendly environmental practices, that exists as a global coalition of eye societies providing education and resources to support sustainable practices in ophthalmology.

Here is a sampling of the ASCRS discussions on the topic.

Greening eye care: reducing ophthalmology’s environmental footprint

The presenters, led by first author Sarishka Desai, BA, described the EyeSustain platform and its 5-pronged mission: educate the global ophthalmic community about more sustainable practices, collaborate with industry to reduce our carbon footprint and surgical waste, support research and innovative solutions that reduce ophthalmology’s environmental impact, support advocacy and education about the public health impact of climate change, and collaborate with industry to reduce our carbon footprint and surgical waste.

Desai, of the University of Connecticut School of Medicine in Farmington, and colleagues presented EyeSustain’s approach to reducing the ophthalmic carbon footprint. She was joined in the study by Nitya Devireddy, BS, MPH, of Penn State College of Medicine in Hershey, Pennsylvania; Sofia Miguez, BA, of Yale School of Medicine in New Haven, Connecticut; and Barbara Erny, MD, of the Department of Ophthalmology at Stanford University in California.

The greenhouse gas data associated with health care are startling. Health care is responsible for 4.4% of all global greenhouse gas emissions, 71% of which arise from the manufacturing, use, and disposal of medical supplies. Ophthalmology has the highest procedural volume of any surgical specialty, with 50 million cataract surgeries expected to be performed globally each year by 2050, Desai reported.

In light of the procedural data, the authors highlighted 6 areas that are currently undergoing research and quality improvement initiatives through the EyeSustain system.

 of cataract surgeons and nurses by David Chang and Cassandra Thiel found that 93% of respondents believe that the trash associated with OR procedures is excessive, and that methods to reduce waste should be identified and implemented.

 encouraged regulatory agencies to allow electronic instructions for use be disseminated in lieu of the traditional paper instructions included with each cataract pack.

Ongoing projects spearheaded by EyeSustain members, including medical students and ophthalmology residents, are taking a look at educating surgeons and surgical staff about sustainability and the impact of OR waste, OR water consumption, and evaluation of flash sterilization associated with cataract surgery.

In recognition of the fact that medications in the OR represent an estimated $560 million in waste annually, a multisociety position paper

 recently formulated 3 key recommendations: topical drugs in multidose containers can be used for multiple patients in surgical facilities if proper guidelines are followed; topical drugs in multidose containers can be used until the manufacturer’s labeled date of expiration if proper guidelines are followed; and, when applicable, patients should be able to take their partially used medication home for postoperative use.

The Aravind Eye Care system’s low-carbon model from Madurai, India, uses alternate energy sources, transport, infrastructure, and equipment maintenance.

 Studying global systems of eye care and waste produced can provide a deeper understanding of the impact of hospitals and providers on climate change, as well as ideas on how western eye care systems can proactively reduce carbon emissions.

The EyeSustain platform includes ophthalmology-specific action steps for greening offices and clinics in collaboration with the 

Partnerships can be established with large manufacturers to reduce packaging, make instruments reusable, and streamline the manufacturing and distribution processes.

In addition to the impact of practice waste on the environment, EyeSustain also recommends studying the effects of climate change on the incidence rates of ophthalmologic conditions, including cataracts, allergic disease, and glaucoma, among others.

Desai and her colleagues recommended that institutions take the following steps:

Conduct a waste audit to quantify the carbon footprint of an institution’s OR emissions. This includes using the EyeSustain-Zasti Carbon Footprint Calculator, using the Sustainability Index for Disposables in Cataract Surgery calculator for cataract packs to evaluate the item-by-item potential for carbon dioxide savings, and surveying clinical staff to identify areas of perceived excess waste.

Identify key stakeholders at an institution and an enthusiastic, multidisciplinary team and completing the OR Sustainability Pledge (

), which has been completed by ambulatory surgery centers/hospital outpatient departments from 9 countries thus far.

Implement best practices; multisociety recommendations for sustainability are easily accessible at eyesustain.org and My Green Doctor for outpatient/clinic resources and local legislation using the American Academy of Ophthalmology Topical Medical Waste Reduction Act legislative template.

Using phacoemulsification waste to guide changes in surgical sustainability

Adjustments to improve the sustainability of ophthalmic surgical practice can have a large impact when scaled to case volume, according to author Margaret Tharp, BSc, who described this study at the ASCRS meeting. She and her coauthors Stella Protopapas, BA, MPH, and Minka Gill, BSc, are from the Indiana University School of Medicine in Bloomington, whereas David J. Palmer, MD, ABO, is from the Northwestern University Feinberg School of Medicine in Chicago, Illinois.

In their study, they sought to draw connections between results from a 24-hour waste audit at an outpatient surgical center and current resources available from EyeSustain to improve the sustainability of ophthalmic surgical practice.

The authors documented the extensive waste generated from 1 day of surgeries in an institution that included 13 phacoemulsification procedures, 5 plastic surgeries, 3 urologic surgeries, and 5 otolaryngologic cases. The waste products were sorted as medications (eg, propofol, eye drop containers), textiles (eg, surgical gowns, drapes), metals (eg, metal wiring, disposable instruments), and plastics (eg, hard, soft, wrappings).

When the amounts of the waste products were tallied, the authors found that “ophthalmology produced the greatest amount of waste in a single day relative to other operating specialties, despite producing the least amount of waste per case. Most ophthalmic waste was from textiles, hard plastics, and medications,” the authors reported.

The specific 13 phacoemulsification procedures resulted in 95.4 lb of waste broken down as follows: 18.5 lb of hard plastic, 5.5 lb of soft plastic, 8.3 lb of wrapping, 13.5 lb of medications, 41.2 lb of textiles, 6.7 lb of miscellaneous waste, and no metals. Compared with other operating specialties, ophthalmology produced the least amount of waste per case but the greatest amount of waste in total due to the relatively high case volume.

It has been reported that “discarded/unused pharmaceuticals from US cataract surgeries demonstrated waste of [approximately] $150 per case while generating carbon dioxide–equivalent emissions that approximated 25,000 to 100,000 flights from San Francisco, California, to Boston annually.

Small changes can have dramatic results. Tharp and colleagues suggested that the following would have positive consequences.

Revising the use of tetracaine bottles intraoperatively; for example, reusing the bottles between cases or sending the bottles home with patients

Optimizing packaging of surgical supplies and electronic instructions

Utilizing intravenous sedation to limit anesthesia gas carbon dioxide–equivalent emissions

Focusing on cutting waste also creates an opportunity to explore the practices of global leaders in sustainable eye care, such as the efforts of the Aravind Eye Hospitals, which provide similar surgical success rates at a fraction of the waste produced by US practices.

Organization eyes green practices, shifting ophthalmology landscape.

L. Neal Freeman

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