South Korean ophthalmologists, led by Seong Woo Kim, MD, PhD, from the Department of Ophthalmology, Korea University Guro Hospital, Seoul, Korea, reported a fungal endophthalmitis outbreak after cataract surgery resulting from contaminated viscoelastic material.

The investigators found that prompt intervention may improve the prognosis of fungal endophthalmitis caused by contaminated medical products.1

Fungal endophthalmitis is rare, occurring in 0.002% of cases in South Korea, according to the Korea Disease Control and Prevention Agency, but it generally follows an intractable clinical course with poor visual prognosis.

An “unusual” outbreak developed in October 2020, that became a nationwide outbreak and was found to be associated with contaminated viscoelastic material (sodium hyaluronate).

Dr Kim and colleagues conducted a retrospective case series analysis of clinical data from multiple institutions across the country from September 1, 2020, to October 31, 2021, to determine the epidemiologic and clinical features and treatment outcomes of this outbreak after cataract surgery.

The authors collected data from surveys conducted in May and October 2021 from the 100 members of the Korean Retinal Society.

The Korea Disease Control and Prevention Agency confirmed that the viscoelastic agent was contaminated.

A total of 265 patients (153 women, 57.7%; 281 eyes; mean age, 65.4 years) were diagnosed with fungal endophthalmitis. The diagnosis fungal endophthalmitis was made a mean of 24.7 days after cataract surgery.

The clinical features of fungal endophthalmitis in the patients included vitreous opacity in 75.4% of eyes, infiltration into the intraocular lens in 50.9%, and ciliary infiltration in 19.6%.

When cultures were performed in 260 of the 281eyes, and fungus was confirmed in 39.6%, and 

All patients were treated with intravitreal antibiotic and antifungal agents with/without pars plana vitrectomy. When vitrectomy was performed, intraocular lenses and lens capsules were removed based on surgeon preference. Postoperatively, all the patients received repeated intravitreal antifungal injections or liposomal amphotericin at least twice weekly, until the infection was considered to be under control. Systemic antifungals also were prescribed for those patients whose infection was not adequately controlled. Patients underwent another surgery if the infection did not response adequately or there was unresponsive inflammation after the repeated intravitreal antifungal injection.

Following treatment, the mean best-corrected visual acuity improved from 0.78 logarithm of the minimum angle of resolution (logMAR) (20/120 Snellen equivalent) to 0.36 logMAR (Snellen equivalent, 20/45 at 6 months.

The investigators also reported that disease remission with no signs of fungal endophthalmitis (or cells in the anterior chamber milder than grade 1) occurred in 214 eyes (93.9%).

They concluded, “The findings of this case series study support the potential benefit of prompt, aggressive surgical intervention that may reduce treatment burden and improve prognosis of fungal endophthalmitis caused by contaminated medical products.”

Kim SW, Kim JH, Choi M, et al. An outbreak of fungal endophthalmitis after cataract surgery in South Korea. 

Published online January 19, 2023; doi:10.1001/jamaophthalmol.2022.5927

Articles

Prompt intervention may reduce treatment burden and improve the prognosis of fungal endophthalmitis after cataract surgery.




Case series study: Managing a fungal endophthalmitis outbreak

The Association for Research in Vision and Ophthalmology (ARVO) announced the winners of its 2023 ARVO Foundation Collaborative Research Fellowship recently.

According to an ARVO news release, Fellows José Arthur Milhomens Filho, MD; Maria Constanza Paz, PhD; Raba Thapa, PhD will each receive up to $10,000 toward their research on a 1-year project. These funds can go towards additional training in specialty equipment or research methodologies.

According to ARVO, the goal of the Fellowship is to pair early-career researchers from developing countries with collaborating scientists in well-established research laboratories to strengthen ophthalmic research capabilities worldwide.

José Arthur Milhomens Filho, MD, is a post-graduate student at the Escola Paulista de Medicina (EPM) - Universidade Federal de São Paulo (UNIFESP), Brazil. Filho plans to use this Fellowship on his research evaluating the levels of the inflammatory molecules in the tear and corneal epithelial cells of keratoconus patients, and if these can be used as biomarkers to identify greater severity and progression of the disease.

"As a native Brazilian, I am the first in my family to follow the area of Ophthalmology, so I am excited to keep pushing forward with my education," Filho said in the ARVO release. "I feel that this award means recognition of the importance of our project which aims to improve understanding of a particular disease with such a huge social impact as keratoconus."

Maria Constanza Paz, PhD, is an assistant researcher at the Centro de Investigación en Bioquímica Clínica (CIBICI)-Consejo Nacional de Investigación en Ciencia y Tecnología (CONICET), Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina. Paz will use the funding to research cellular and molecular mechanisms triggered by alpha2-Macroglobulin (a2M) in retinal neurodegeneration, an area in which little is currently known.

Thanks to the Fellowship, Paz said it "will enable development of novel therapeutic approaches, more specific and fit-for-the-purpose related with the ability to modulate autophagic flux and/or the deleterious effect of a2M."

Raba Thapa, PhD, is an associate professor of ophthalmology at the National Academy of Medical Sciences and a consultant vitreo-retinal surgeon at the Tilganga Institute of Ophthalmology, Nepal. Thapa will use the funding to explore the prevalence, pattern, and associated factors for retinal diseases among the population residing in high altitudes, since retinal diseases are the major cause of blindness in Nepal.

"The findings of the study will help to develop appropriate strategies in the future among the high-risk people to reduce the avoidable blindness from retinal diseases," said Thapa. “I am very grateful to the ARVO Foundation... This award will certainly help to boost my career in research works, networking and collaborations in the future for many needful research works in the field of ophthalmology and visual science for helping in reducing blindness especially to those living in remote areas and at low middle income countries. The research findings will also help for policy makers and other stakeholders working in reducing blindness globally."

For more information on the ARVO Foundation Collaborative Research Fellowship, visit 

Three recipients will each receive up to $10,000 toward their research on a 1-year project that can go toward additional training in specialty equipment or research methodologies.

Winners of 2023 ARVO research fellowships announced

An iris-fixed intraocular lens (IOL) resulted in a significant decrease in endothelial cell density (ECD) 2 years after explantation,1 according to Tae Young Kim, MD, and colleagues. Dr Kim is from the Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, and the Department of Ophthalmology, Gangnam Severance Hospital, Yonsei University College of Medicine, both in Seoul, Korea.

The research team retrospectively studied the long-term corneal endothelial cell changes and visual outcomes after this iris-fixated phakic IOL was explanted in patients with endothelial damage and investigated any potential predictors of endothelial injury.

All patients had a corneal ECD below 2,000 cells/mm2 at the time of the procedure and were treated between April 2016 and October 2020. The primary study outcome was the change in corneal endothelial parameters, including ECD, over the long-term follow-up, the authors explained. Secondary outcomes included the changes in the corrected-distance visual acuity (VA) and analysis of prognostic factors.

Twenty-eight patients (44 eyes; average age, 42.5 ± 7.8 years; range, 27–63) were included in the study. The mean ECD before IOL explantation was 1,375.4 ± 468.2 cells/mm2 (range, 622–1,996), and the average duration of follow-up after explantation was 20.5 months (range, 6–58.2).

Two years after explantation, the researchers reported a more than 25% decrease in the ECD to 1,019.6 ± 368.6 mm2 (range, 608–1,689) (p< 0.01).

They also reported no significant change in the corrected-distance VA (20/23–20/22) (p = 0.59).

They found that a longer surgical duration (odds ratio, 1.004) (p= 0.04) was the only significant factor that was weakly associated with the postoperative decreases in the ECD.

They concluded that although the ECD continued to decrease despite phakic IOL explantation on a long-term follow-up, “patients did not experience any discomfort or showed decreases in VA. Therefore, a careful follow-up is required for possible endothelial injury after phakic IOL explantation.”

Kim TY, Moon IH, Park SE, et al. Long-term follow-up of corneal endothelial cell changes after iris-fixated phakic intraocular lens explantation. 

Research team suggests careful follow-up is required for possible endothelial injury.

Corneal ECD decrease continues after iris-fixated phakic IOL explantation

An international team of investigators, led by Emma Pead, reported that changes in the vasculature of the peripheral retina may hold clues to the development of cognitive impairment and may be useful surrogate measures of cognitive decline.

The study found differences in the retinal vasculature in patients with Alzheimer’s dementia and mild cognitive impairment. She is with the VAMPIRE Project, Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK.

She and her colleagues conducted a pilot study in which they used ultra-widefield retinal imaging to assess the presence of abnormalities in the retinal vasculature in patients with Alzheimer's dementia and mild cognitive impairment (MCI) and compared them with participants with normal cognition.

A total of 103 individuals were included in the study: 28 had Alzheimer’s dementia, 30 mild cognition impairment, and 45 normal cognition. The images obtained from the patients underwent analysis to quantify the retinal vascular branching complexity, width, and tortuosity, Ms. Pead explained.

The investigators reported increased vessel branching in the midperipheral retina and increased arteriolar thinning in those with Alzheimer's dementia. Increased rates of arteriolar and venular thinning were seen in patients with mild cognitive impairment as well as a trend toward decreased vessel branching.

The investigators concluded thatthe distinct cognitive states showed significant differences in the retinal vasculature in the peripheral retina. However, they also advised that larger studies are needed to establish the clinical relevance of their findings.

They believe that ultra-widefield imaging may be a promising technology for assessing larger areas of the retinal vasculature to uncover retinal changes in Alzheimer’s disease.

Pead E, Thompson AC, Grewal DS, et al. Retinal vascular changes in Alzheimer’s dementia and mild cognitive impairment: a pilot study using ultra-widefield imaging. 

Ultra-widefield imaging may be a promising technology for assessing larger areas of the retinal vasculature to uncover retinal changes in Alzheimer’s disease, according to investigators.

Finding the clues: What retinal vasculature changes may mean for cognitive impairment

Herpesvirus DNA was discovered in a high percentage of corneal grafts after transplantation, which underscores the need for routine herpes simplex virus (HSV-1) and varicella zoster virus (VZV) PCR testing in all explanted corneas according to Julia Bing Bu, MD, and colleagues from the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

“Graft failure after penetrating keratoplasty (PK) is a serious complication, especially in eyes with herpetic keratitis (HK),” the authors commented.

Dr Bu and colleagues retrospectively evaluated the prevalence and graft survival of HSV-1 and VZV DNA in recipient corneas during PK between January 2020 and June 2021. They performed polymerase chain reaction (PCR) on all excised corneal buttons regardless of the primary clinical diagnosis.

A total of 112 consecutive patients (112 eyes) who underwent PK were included in the study. When PK was performed, 91 (81.25%) patients had no history of HK and the 21 (18.75%) remaining patients did have a history.

Of the 91 with no history of HK, in 12 (13.2%) eyes, the recipient corneas were positive for HSV-1 DNA, 3 (3.3%) eyes tested positive for VZV DNA, and in 2 (2.2%) eyes tested positive for both.

Among the 21 eyes that were positive for HK preoperatively, the recipient corneas tested positive for HSV-1 DNA in 13 (61.9%) eyes and VZV DNA in 1 (4.8%) eye. All patients with positive herpes DNA tests and no history of HK before they underwent PK were treated with antiherpetic drugs and had a 100% graft survival rate after 1 year.

The authors concluded, “We found herpesvirus DNA in 18.7% of recipient corneas without clinical suspicion or history of herpes keratitis. This suggests the need for routine HSV-1 and VZV PCR testing in all explanted corneas regardless of clinical suspicion to detect, treat, and prevent possible recurrence of herpes infection in corneal grafts and support graft survival.”

Bu JB, Grabitz SD, Pfeiffer N, Wasielica-Poslednik J. Prevalence of herpesvirus DNA in corneal transplant recipients. 

Recent research suggests the need for routine HSV-1 and VZV PCR testing in all explanted corneas regardless of clinical suspicion to detect, treat, and prevent possible recurrence of herpes infection in corneal grafts and support graft survival.

Identifying herpesvirus DNA in corneal grafts

An innovative technology used to treat glaucoma at the same time as cataract surgery (ELIOS) is now registered for use in the United Kingdom.

The technology uses excimer laser energy to create microscopic openings in the trabecular meshwork to re-establish the natural flow of aqueous.

It does not require an implant and provides long-lasting results that may free patients and their doctors from the demands of drop therapy, said the company in a prepared statement.

“Multiple clinical studies across Europe have demonstrated that ELIOS has a strong efficacy and safety profile, with significant advantages over other forms of microinvasive glaucoma surgery (MIGS),” said Elliot Friedman, chief executive officer of Elios Vision.

“Cataract surgery is an opportune time to improve glaucoma control and especially to reduce the medication burden in those on chronic therapy. ELIOS’ excimer laser technology removes TM tissue with minimal surgical trauma, minimizing the healing response and avoiding the need to place an implant. This makes ELIOS a very attractive option at the time of cataract surgery,” said Prof Keith Barton, Consultant Ophthalmologist, Moorfields Eye Hospital, London.

Elios Vision announces ELIOS registration in the  United Kingdom

Polish investigators who conducted a review of the occurrence of ophthalmic complications in inflammatory bowel disease (IBD) reported that ocular disorders are the third most common manifestation of the disease, and advised physicians to perform ophthalmic evaluations,

 according to the lead study author is Wiktoria Pytrus, MD, from Ophthalmonology Clinical Centre SPEKTRUM, Wroclaw, Poland.

The investigators explained that while the clinical manifestations of IBD, which include Crohn’s disease and ulcerative colitis, are primarily in the gastrointestinal tract, about 25% of patients are affected by extraintestinal complications and these include eye diseases. Musculoskeletal and mucocutaneous involvement are seen most often after the gastrointestinal tract and ocular diseases follow.

Their primary findings include the following. “Episcleritis, frequently occurring in IBD patients, may be associated with exacerbation of the intestinal disease. Uveitis does not correlate with IBD activity but may be related to the presence of other extraintestinal manifestations, particularly erythema nodosum and peripheral arthritis. Early detection and specific therapy of ocular manifestations of IBD are fundamental to avoiding sight-threatening complications,” Dr Pytrus and colleagues reported.

Specifically, they found that ocular symptoms are seen in from 0.3% to 13% of all patients with IBD, in patients with ulcerative colitis from 1.6% to 5.4% and in Crohn’s disease from 3.5% to 6.8%. Episcleritis occurs in 2% to 5% and anterior uveitis in 0.5% to 3.5% of patients with IBD.

Regarding treatment, systemic corticosteroids or immunosuppressants may be necessary in patients with severe disease to control the ocular inflammation. Persistent and relapsing conditions usually respond well to tumor necrosis factor-α-inhibitors.

The researchers emphasized the importance of collaboration between gastroenterologists and ophthalmologists to ensure that patients are treated appropriately.

They concluded, “Ocular involvement in IBD is a rare extraintestinal manifestation, but it may be critical because of its potential sight-threatening complications if not treated promptly and accurately.”

cicka A. A review of ophthalmic complications in inflammatory bowel diseases. 

2022;11:7457. https:// doi.org/10.3390/jcm11247457

Ocular involvement in IBD is a rare extraintestinal manifestation, but may be critical because of its potential sight-threatening complications if not treated promptly and accurately, according to researchers.

Why patients with inflammatory bowel disease might need to see their ophthalmologist 

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have different retinal and choroidal microvascular findings compared with healthy controls, including a decreased mean vessel density at the deep vascular complex of the macula and a decreased mean subfoveal choroidal thickness, Dr Przemysław Krajewski, PhD, reported.

Dr Krawkewski, who is from the Ophthalmology Department, Infant Jesus Teaching Hospital, Medical University of Warsaw, Warsaw, Poland, and colleagues conducted an observational clinical cohort study

 to investigate the microvascular retinal and choroidal changes associated with CTEPH in patients compared with healthy control subjects.

The study included 36 patients (72 eyes) with CTEPH and 65 healthy control subjects (130 eyes). Optical coherence tomography (OCT) and OCT angiography images were obtained from each participant using the AngioVue Imaging System (Optovue, Inc., Freemont, California, USA).

The research team reported a few differences in the patients with CTEPH that included a decreased mean vessel density at the deep vascular complex of the macula, a decreased mean subfoveal choroidal thickness, and an increase in the size of the foveal avascular zone.

In patients with CTEPH who had at least one systemic disease such as arterial hypertension, diabetes, chronic coronary syndrome, and/or hyperlipidemia, the range of the vascular complications increased. When a comorbidity was present there was an accompanying decrease in the mean vessel density in the superficial vascular complex of the macula, excluding the fovea, and a decrease in the mean vessel density in the radial peripapillary capillary plexus, the investigators reported.

The investigators theorized that measuring the foveal avascular zone and the vessel density of the deep vascular complex and subfoveal choroidal thickness may be useful and sensitive predictors of impaired retinal and choroidal circulation in patients with CTEPH without a systemic disease.

Krawjewski P, Turczyńska M, Gołębiewska J, et al. Optical coherence tomography angiography findings in patients with chronic thromboembolic pulmonary hypertension. 

. 2022;42:2354-360; doi: 10.1097/IAE.0000000000003607

The research team reported a few differences in patients that included a decreased mean vessel density at the deep vascular complex of the macula, a decreased mean subfoveal choroidal thickness, and an increase in the size of the foveal avascular zone. 

Imaging shows ocular changes in chronic thromboembolic pulmonary hypertension

Injection of heavy silicone oil to treat persistent, full-thickness macular holes is safe and effective. The preoperative best-corrected visual acuity (BCVA) and the minimum linear diameter may predict the anatomic success,

 according to Dr Tibor Lohmann, MD, lead author from the Department of Ophthalmology, RWTH Aachen University, Aachen, Germany.

Dr Tibor and colleagues retrospectively studied 63 eyes with persistent, full-thickness macular holes after they underwent a primary pars plana vitrectomy and internal limiting membrane peeling; the patients then underwent a secondary surgery during which heavy silicone oil tamponade was used to close the hole. During follow-up the macular status was evaluated on spectral domain optical coherence tomography and the BCVA was measured.

The purpose of the study was to determine the anatomic success and the BCVA with use of the heavy silicone oil as a tamponade.

The surgeries were successful anatomically in 50 (79.4%) of the 63 study eyes. In those 50 eyes, the BCVA before the first vitreoretinal surgery was significantly better compared with the eyes in which anatomic success was not achieved, respectively, 0.77 ± 0.24 (range, 1.3–0.3; ∼20/125 Snellen) logarithm of the minimum angle of resolution (logMAR); and 0.88 ± 0.17 (range, 1.1–0.6) logMAR; ∼20/160 Snellen) (P = 0.044).

In addition, in the eyes that achieved anatomic success compared with those that did not, the minimum linear diameter of the full-thickness macular holes was significantly smaller before the primary surgery, respectively, 403.4 ± 128.7 µm (range,199.0–707.0) and 568.1 ± 209.1 µm (range, 307.0–953.0); (P = 0.009) and the secondary surgery, respectively, 464.1 ± 215.0 µm (range, 178.0–1,521.0) and 663.3 ± 228.5 µm (range, 451.0–1,301.0) (P = 0.010).

The BCVA did not improve in patients who remained phakic during all surgeries, despite achieving anatomic success.

The study concluded, “Heavy silicone oil tamponade in a secondary surgery for persistent full-thickness macular holes is a safe and efficient surgical method. The BCVA and minimum linear diameter before surgery may be indicators for anatomical success.”

Lohmann T, Schwarzer H, Koutsonas A, et al. Treatment of persistent macular holes with heavy silicone oil. 

 2022;42:2258-66; doi: 10.1097/IAE.0000000000003620

Best-corrected visual acuity and minimum linear diameter before surgery may be indicators for anatomical success.

Treating persistent macular holes with heavy silicone oil

Investigators reported that overweight/obesity, migraine, asthma, and smoking may be major risk factors for ocular hypertension (OHT) conversion to open-angle glaucoma (OAG) in their analysis of a Spanish and Portuguese population.

Lead authors Caroline Garcia-Villanueva, MD, from the Ophthalmic Research Unit Santiago Grisolia, Foundation for Research in Health and Biomedicine, the Cellular and Molecular Ophthalmobiology Group, Surgery Department, Faculty of Medicine and Odontology, University of Valencia, and the Department of Ophthalmology, University General Hospital, Valencia, Spain, and Elena Milla, MD, fromthe Department of Ophthalmology, Clinic Hospital, Barcelona, Spain, and the Spanish Net of Ophthalmic Pathology OFTARED, Institute of Health Carlos III, Madrid, reported their findings in the 

They explained that many unanswered questions remain about the course of OAG, the most prevalent type of glaucoma and if nutritional or toxic habits, personal characteristics, and/or systemic diseases affect the disease course.

To answer this, the investigators undertook a multicenter analytical, observational, case–control study that included 412 participants (age range, 40–80 years) who had OHT or OAG. The primary endpoint was to determine an association between specific lifestyle habits; anthropometric and endocrine–metabolic, cardiovascular, and respiratory events; and commonly used psychochemicals, in these Spanish and Portuguese patients.

The researchers collected and analyzed demographic, epidemiologic, and ocular/systemic clinical data from all patients. The mean patient age was 62 ± 15 years, and the majority ranged in age from 67 to 80 years.

Data analysis showed that the central corneal thickness-adjusted intraocular pressures in each eye were 20.46 ± 2.35 and 20.1 ± 2.73 mmHg for patients with OHT and 15.8 ± 3.83 and 16.94 ± 3.86 mmHg for those with OAG. The comparisons reached significance (p = 0.001).

“The highest prevalence rates of the surveyed characteristics in both groups were for overweight/obesity and daily coffee consumption followed by psychochemical drug intake, migraine, and peripheral vasospasm. Our data showed that overweight/obesity, migraine, asthma, and smoking are major risk factors for conversion from OHT to OAG in this Spanish and Portuguese population,” the investigators reported.

They concluded, “In this Spanish and Portuguese cohort, we identified some non-ocular-specific factors to help assess the risk of OAG and to prevent or delay glaucomatous optic nerve degeneration and blindness. Based on the results of this study, we strongly recommend careful and considered care for the people suffering from these disorders to prevent subsequent visual disability and loss of quality of life.”

Garcia-Villanueva C, Milla E, Bolarin JM, et al. Impact of systemic comorbidities on ocular hypertension and open-angle glaucoma, in a population from Spain and Portugal. 

Investigators' data showed that overweight/obesity, migraine, asthma, and smoking are major risk factors for conversion from ocular hypertension to open-angle glaucoma in this Spanish and Portuguese population.

How systemic comorbidities may affect conversion from OHT to OAG

A common neurodegenerative disorder, Alzheimer disease (AD) is typically diagnosed symptomatically because of the high cost and invasiveness of alternative methods like positron emission tomography scans and lumbar punctures. With the identification of microvascular and neurosensory structural alterations in the retinas of individuals with AD, non-invasive retinal imaging may be an adjunctive or even an alternative means of detecting AD early.

To test this possibility, the Eye Multimodal Imaging in Neurodegenerative Disease (iMIND) lab at Duke University applied modern machine learning techniques to retinal images and clinical patient data, as shared in their recent publication in the 

 The model was able to distinguish those with symptomatic AD from cognitively normal controls, serving as a proof of concept for using the retina as a “window to the brain” and exhibiting promise for artificial intelligence (AI) as a powerful tool in the diagnosis of AD.

For this study, the iMIND team collected and used the following types of retinal images: ganglion cell-inner plexiform layer (GC-IPL) thickness colour maps from optical coherence tomography (OCT), superficial capillary plexus en face 3 × 3 mm and 6 × 6 mm OCT angiography (OCTA) images centred on the fovea, ultra-widefield (UWF) scanning laser ophthalmoscopy (SLO) colour fundus photos, and UWF SLO fundus autofluorescence images.

In addition to the raw images, subjects’ age, sex and visual acuity as well as quantitative metrics of retinal microvasculature and structure from the OCT and OCTA scans were included.

The ground truth (AD or cognitively normal) was determined by a team of expert neurologists; participants with underlying conditions, which could bias the detection accuracy, were excluded from the study.

The images were manually assessed for quality prior to adding to the input dataset. Poor-quality images were excluded and the UWF images were cropped to a standardised region of interest to avoid or remove artifacts, yielding high-fidelity data.

When imaging data are the primary input for a machine learning model, one of the most powerful and commonly used subtypes of machine learning is a convolutional neural network (CNN), which employs hierarchical learning to assimilate the complexities of images and spatially inconsistent features.

CNNs decompose image inputs into more basic visual features such as lines and edges, which can themselves combine to form shapes that in turn can combine to form groups of shapes. Each of these steps is referred to as a “layer” of the CNN.

By simplifying a complex problem into several simple problems, the model can efficiently learn the proper way to extract the useful features and biomarkers from images.

With a dataset of 222 eyes from cognitively normal patients and 62 eyes from AD patients, the team divided the data into training, validation and testing sets for the model.

The training set included 34 AD and 152 cognitively normal eyes (18.3% AD) whereas the validation set included 6 AD and 24 cognitively normal eyes (20.0% AD).

The test set included 22 AD and 46 cognitively normal eyes (32.3% AD) that were accrued a year after the training and validation images by different imagers using the same imaging machines. A model should be capable of accurate predictions using images collected by photographers different from those who supplied its training dataset.

The model was initially trained on the training set and had its parameters adjusted by feedback from the area under the receiver operating characteristic (AUC) and accuracy metrics when tested against the validation set.

After adjustments were finalised, the model was trained on both the training and validation data and tested against the test set (data not seen during any part of the training or parameter adjustment process). Eleven models differing in their combinations of inputs were trained and tested, and their scores reported with the AUC metric.

The model using GC-IPL maps, quantitative OCT and OCTA data, and patient data achieved the best-performing peak average AUCs of 0.861 (95% confidence interval [CI] 0.727, 0.995) on the validation set and 0.841 (95% CI 0.739, 0.943) on the test set.

This performance was impressive, especially when considering it had been trained on a small dataset. Increasing the size of the dataset could yield even better performance for predicting AD using retinal images and related metrics.

The CNN model made significantly accurate predictions for the presence of symptomatic AD via retinal imaging and clinical data, providing an excellent proof of concept. The project illuminated the capabilities of using the retina to detect AD, showing promise for AI detection that, if developed, could serve as a non-invasive means of screening and expand patient access to care.

Although the data were curated meticulously and filtered for quality and ocular artifacts, the dataset was relatively small and did not assess racial diversity.

The AD model was limited to data collected from AD patients enrolled from the Duke Memory Disorders Clinic and cognitively normal participants from the Duke Alzheimer Disease Research Center or community volunteers aged 50 years or older. As a result, 284 eyes were used: 222 from cognitively normal participants and 62 from participants with symptomatic AD.

Having significantly more distinct data points would further improve the designed model’s ability to generalise and make more accurate predictions. Understandably, the high-quality dataset was small but leaves room for improvement in future models. The struggle of any machine learning venture is robust data, and image and data inputs from diverse populations will need to be incorporated in future AD detection efforts.

The iMIND team took several measures to ensure that a primary challenge in machine learning, overfitting, was avoided.

Overfitting is when a model learns to associate ungeneralisable details with the output. More specifically, when the model associates a participant’s images, quantitative and patient data with the output rather than learning what features of the inputs across the entire dataset accurately contribute to the output.

Instead of creating a CNN feature extractor for each imaging modality, a modified, parsed ResNet18 was used, reducing the trainable weights to one-third of what they could have been. The team’s model was especially prone to overfitting because of the small dataset, which could cause the model to memorise the images associated with a certain output as opposed to learning the features of the inputs predictive of the output (AD or not AD).

Having fewer parameters reduces the possibility of overfitting when paired with techniques such as regularisation (penalises the learning of complex, noisy features), which the team employed. More data would enable the exploration of a larger model to assess whether a slight increase in complexity would improve overall accuracy in detecting AD without the issue of rapid overfitting on small datasets.

Future steps for this CNN model would be to acquire a larger, more diverse population to ensure a greater density of sample points for the model to learn from, improving the model’s generalisability. Increasing the dataset with more high-quality images would yield the highest return on prediction accuracy and would additionally offer the ability to assess the benefits of an augmented model size.

Future efforts should focus on AD detection in patients with underlying conditions that also impact retinal imaging, such as diabetes and glaucoma, as well as using different imaging formats because image standardisation is still evolving across imaging platforms in ophthalmology.

Notably, the automation of quality assessment procedures is a crucial task to facilitating future endeavours, as manually determining the quality of images and filtering for high-quality images are time- and resource-intensive tasks.

Duke University’s interdisciplinary team at iMIND lab established the potential of machine learning to detect symptomatic AD and the ability to use retinal imaging paired with numerical and categorical data for the task. The effort yielded an important proof-of-concept model, expounding promise for AI application in this exciting field.

David Bearden; Terry Lee, MD; Alex Richardson; C. Ellis Wisely, MD, MBA; Ricardo Henao, PhD; Dilraj S. Grewal, MD, FASRS; Sharon Fekrat, MD, FASRS

The authors are part of the interdisciplinary iMIND AI team, which investigates the use of multimodal retinal and choroidal imaging to identify neurodegenerative disease using AI at Duke University, Durham, North Carolina, US. No author has any financial declaration relevant to the article.

Heringa SM, Bouvy WH, Van Den Berg E, et al. Associations between retinal microvascular changes and dementia, cognitive functioning, and brain imaging abnormalities: A systematic review.

Wisely CE, Wang D, Henao R, et al. Convolutional neural network to identify symptomatic Alzheimer’s disease using multimodal retinal imaging. 

An interdisciplinary team at Duke University has developed a proof-of-concept machine learning model capable of detecting symptomatic Alzheimer disease using multimodal retinal imaging data.

Retinal imaging to detect Alzheimer disease: machine learning model

Dementia is a progressive deterioration in cognitive function not related to normal ageing and secondary to different diseases. It results from various diseases and injuries affecting the brain. The most commonly affected areas include memory, visuospatial function, perception, orientation, language, attention and problem solving.

The progression of the manifestations is usually slowly deteriorating, but it changes depending on the different types of dementia. The manifestations include behavioural and psychological symptoms. Behavioural symptoms include agitation, restlessness, inappropriate conduct, sexual disinhibition and aggressiveness. Psychological symptoms include depression, hallucinations and delusions, apathy and anxiety.

 There is no cure for dementia, even with nonpharmacologic and pharmacologic management. Nonpharmacologic management includes physical activities, social stimulation, intellectual activities, exercise and socialisation. Pharmacologic treatment may offer limited improvement in Alzheimer and Parkinson disease.

The main cause is the increase in the aging population. In Europe, more than one-fifth is older than 65 years, and the life expectancy is 81.3 years. The prevalence of dementia is related to aging, from 60 to 64 years is 0.6%; 65 to 69 years is 1.3%; 70 to 74 years is 3.3%; 75 to 79 years is 8%; 80 to 84 years is 12.1%; 85 to 89 years is 21.9%, and older than 90 years is 40.8%.4 In Europe, the number of people living with dementia is estimated to be 9,780,678: 6,650,228 women and 3,130,449 men, representing 1,9% of the total population. The number of people with dementia in Europe will nearly double by 2050, increasing to 18,846,286.

Cataracts are the number one cause of preventable blindness, causing worldwide advanced vision loss in 65.2 million people and blindness in 20 million. Their prevalence increases with age, ranging from 4% at ages 55 to 64 to 92% at age 80 and older. Cataract surgery is the most effective and common procedure in all medicine. More than 30 million people undergo the surgery every year.

Europe has a population of more than 513.5 million, performing annually 4.7 million cataract surgeries. Different areas and countries have different demographic distributions and access to surgery, realities, and resources. Most countries performed 1.000 surgery or more per 100.000 inhabitants, but others were doing less than 400 surgeries,

Lee studied prospectively 3038 adults 65 years or older with cataracts and followed up until the development of dementia. The patients who received cataract surgery had 30% less risk of dementia for 10 years.

Cataract surgery can improve symptoms of dementia by enhancing visual acuity and secondary visuospatial orientation-related dementia test results. In addition, patients with dementia and poor vision often have a more active lifestyle after cataract surgery. Patients previous to cognitive impairment and with it may benefit in the short and long term. Assessing the visual function of patients is a key factor, and considering cataract surgery when appropriate may help reduce the risk of dementia.

 Considering the benefits of cataract surgery, even in dementia, it is critical to do more research on the topic, evaluate big data and make cost-analysis cases.

There is much work to do to prevent dementia. Forty percent of dementia cases are preventable considering numerous factors, including correcting sensory impairments, having social connections, good education, regular physical activity, reducing obesity and diabetes, BP control, reducing air pollution, preventing head injury, limiting alcohol and avoiding smoking.

It is considered that 1.8% of dementia cases are associated with vision impairment.

 Eighty-percent of vision impairment occurs in adults aged 50 years and older, and 90% of cases are preventable, with cataracts being a crucial factor.

 With this evidence, we have more reasons to promote cataract surgery in the older population with dementia risk.

Cataract surgery on time is an efficient option for our patients to facilitate an independent life, better care and fewer costs. From the public healthcare perspective, the cost of the operation is minimal compared with the costs of dementia, that range from 2,687 EUR to 15,468 EUR per individual every year.

 Public authorities have to be aware of the importance of cataract surgery to benefit patients and communities and offer more resources.

March de Ribot is an ophthalmology consultant at Girona and Otago University, Spain. He has no relevant financial disclosures.

Dr Bilgic is an ophthalmology consultant at Alpha Vision Augenarzt Practice in Bremerhaven and Dorum, Germany. He has no relevant financial disclosures.

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The procedure facilitates an independent life, better care and fewer costs.

Considering cataract surgery and reduction of dementia in Europe

According to Ruth Williams, hypertension plays a key role in glaucoma, and it has the potential to be a modifiable risk factor.

Hypertension plays a key role in glaucoma, and it has the potential to be a modifiable risk factor, according to Ruth Williams, MD, who discussed the topic during a presentation at the 27th annual Glaucoma Symposium during Glaucoma 360 at the Westin St. Francis San Francisco on Union Square.

Williams is a glaucoma consultant and president emeritus of the Wheaton Eye Clinic in Wheaton, Illinois.

“Blood pressure is also (sometimes) a modifiable risk factor for glaucoma,” she said.

Currently, the IOP is the only modifiable factor but clinicians should be aware of the effects of low BP.

Normal tension glaucoma, she explained, is chronic, progressive optic neuropathy that results in a characteristic optic nerve head cupping, retinal nerve fiber layer thinning, functional visual field loss, and “normal” IOPs.

Flammer syndrome is a pathology that can cause normal tension glaucoma and is characterized by cold hands and feet, low body mass index, and is often associated with low blood pressure (BP). An ocular sign is the reduced ability to autoregulate the ocular blood flow.

A representative case is that of a 57-year-old Caucasian woman with a baseline IOP of 16 mmHg. The patient has cold hands, Raynaud’s syndrome, migraines, low BP, and sleep apnea. Magnetic resonance imaging showed normal head and orbital findings. The patient was generally healthy, took vitamins and was treated for dermatitis. The central corneal thicknesses were 592 and 584 microns. Her bilateral IOPs at night were 10 mm Hg consistently.

In patients with Flammer syndrome, the nocturnal BP tends to be lower. In patients whose BPs dip more than normal, the glaucoma progresses.

This variability in the BP can cause end-organ damage in the heart, kidney, brain, and optic nerve.

There is good evidence from multiple population-based studies for physicians to consider low BP and low ocular perfusion pressure (OPP), defined as 2/3 (mean arterial pressure – IOP), in which there may be inadequate blood flow to tissues, as risk factors for POAG, in that a lower diastolic BP was associated with a 2 to 6 times higher risk of POAG developing.

“A strong association has been seen between low OPP and the incidence/prevalence of OAG,” she commented.

 showed that a lower mean arterial pressure, defined as the diastolic BP + 1/3 (systolic BF-diastolic BP), and lower diastolic arterial pressure led to faster rates of loss of the retinal nerve fiber layer in patients with similar IOPs, suggesting that the levels of systemic BP may be a significant factor in glaucoma progression.

 showed that of 20,815 patients analyzed, 462 developed POAG. This study implicated vascular dysregulation as a potential cause of OAG, and that the BP medications did not stop POAG development.

Williams urged physicians to be aware of the potential impact of low BP in patients with glaucoma.

1. Jammal AA, Berchuck SI, Mariottoni EB, et al. Blood pressure and glaucomatous progression in a large clinical population. 

. 2022;129:161-70. doi: 10.1016/j.ophtha.2021.08.021.

2. Lee EB, Hu W, Singh K, Wang SY. The association among blood pressure, blood pressure medications, and glaucoma in a nationwide electronic health records database. 

Ruth Williams, MD, explained the importance of hypotension in glaucoma and its potential as a modifiable risk factor at the 27th annual Glaucoma Symposium during Glaucoma 360 at the Westin St. Francis San Francisco on Union Square.