Each year, the Association for Research in Vision and Ophthalmology (ARVO) annual meeting gifts the eye care profession with a cornucopia of new research that lets us see where the winds are blowing clinically. Here, we’ve compiled research specific to cornea and contact lens care we feel may be most impactful for practicing optometrists. 

This year, the meeting opted for a hybrid format after an all-virtual conference in 2021, gathering in Denver May 1-4 and streaming virtually May 11-12. The theme of ARVO 2022 was “accelerating discovery through team science.” The findings summarized here are only a snippet of those presented at the meeting, but show the rich expanse of insights ARVO generates each year.

Cornea

Many teams of researchers presented their findings on treatments focused on this part of the eye.

• Multidrug-resistant Staphylo-coccus. In a recent study examining common ocular antibiotics’ susceptibilities toward Staphylococcus, researchers collected 67 isolates from patients. The antibiotics examined in the study included levofloxacin, tobramycin, clindamycin fusidic acid and cefazolin sodium. Cefazolin sodium and fusidic acid were reliable options for managing this condition in the ocular surface.^-1 

“Our results indicate that cefazolin sodium and fusidic acid may be considered a reliable alternative for the treatment of multidrug-resistant Staphylococcus in the ocular surface, especially of beta-lactamase drug-resistant Staphylococcus,” the study authors noted in their abstract.

The major isolate in the eyelid margin and conjunctival sac was drug-resistant Staphylococcus epidermidis. Drug-resistant Staphylococcus aureus was the major isolate in the lacrimal sac and cornea, according to the abstract. Also, the susceptibility of cefazolin sodium and fusidic acid against beta-lactamase isolates were higher when compared with methicillin-resistant isolates.

“Multi-drug resistant Staph. remains a major clinical practice concern. Fortunately, earlier generation cephalosporins (in particular cefazolin sodium) are still very effective for treating these infections,” says Joseph Shovlin, OD, of Northeastern Eye Institute in Scranton, PA. “Combining cefazolin sodium and fusidic acid appears to be a reliable alternative to vancomycin.”

• Impact of hormones on keratoconus. In a recent study, researchers sought to establish the relationship between sex hormones and their receptors in healthy and keratoconus corneal stromal cells. The study authors used a 3D in vitro self-assembled extracellular matrix model. The in vivo analysis measured androgen/estrogen ELISA expression before and after corneal crosslinking (CXL) among a small cohort of patients with keratoconus.²

Estrone and estriol stimulation among healthy women revealed significant up-regulation of the androgen receptor, progesterone receptor and estrogen receptor beta compared with healthy men. The data also showed higher expression of estrogen receptor alpha and estrogen receptor beta in women with keratoconus vs. their male counterparts.

“Systemic and local hormonal levels may be important biomarkers in the assessing treatment options for keratoconus,” Dr. Shovlin notes.

Following CXL, DHEA sulfate levels were lower while estrone and estriol levels were higher. These in vivo findings indicate this treatment affects the corneal tissue and modulates hormonal levels in the bloodstream.

“Our data suggests that the human cornea is a sex-dependent and a hormone-responsive tissue. We posit that keratoconus is a systemic disease, at least initially, and is heavily dependent on systemic and local hormone alterations,” the study authors concluded in their abstract.

• Ocular bacteria and HSK treatment. An ocular bacterium that produces immune-regulating cytokines that could one day be used to limit the inflammation effects of vision-threatening herpes stromal keratitis (HSK).³ 

A team of researchers from the University of Pittsburgh hypothesized, “Delivering IL-10 using a genetically modified ocular commensal, Corynebacterium mastitidis (C. mast), will reduce immunopathology associated with HSK.”

The team found that the genetically engineered bacteria were able to produce and secrete functional murine IL-10. They explained, “IL-10 from C. mast regulates T-cell responses by suppressing proliferation and IFN-γ production. Conversely, IL-10 from C. mast does not affect IL-17, which prevents C. mast from becoming a pathobiont.” Therefore, this ocular therapeutic appeared to successfully reduce HSK in vivo.

The team concluded, “This study illustrates the first steps in engineering an ocular bacterium that can control excessive inflammation at the ocular surface.”

• Corneal guttata in Hispanic cohort. Are some populations more vulnerable to corneal endothelial compromise than others? Researchers in Mexico recently assessed the central corneal specular microscopy of healthy Hispanic adults and found a high prevalence of corneal guttata, outgrowths of Descemet’s membrane produced by distressed endothelial cells, with a higher preponderance in females.⁴ 

The study included 702 eyes from 356 patients (55% female). The mean age was 70. The researchers considered endothelial pleomorphism if <50% of cells were hexagonal and polymegethism if the coefficient of variation was >40%.

Mean endothelial cell density and cell hexagonality in this Hispanic population was lower than in other reports. The study determined that 76% of the patients had a pleomorphic endothelium, with a significant difference in cell hexagonality between male and female patients. 

Researchers are developing an ocular bacterium that is able to produce and secrete functional murine IL-10, regulating T-cell responses and reducing inflammation in HSK patients. Photo: Alexander Martinez, OD. Click image to enlarge.

Also, 48% of patients had polymegethism, and 18% had corneal guttata, with 64% of the corneal guttata patients being female.

“Morphologic characteristics appears to be a more viable marker for cell function than even the actual number of endothelial cells for maintaining corneal transparency,” Dr. Shovlin proposes.

“Knowing the average endothelial parameters in our population can allow us to predict whether the endothelial pump function will tolerate surgery performed on the eye before affecting corneal transparency,” the researchers wrote in their abstract.

• RCE characteristics. Recurrent corneal erosion (RCE) presents a long-standing challenge, with patients experiencing a wide range of symptoms and cure rates. To better define its epithelial symptomatology and evaluate the subjective efficacy of proposed treatments, researchers queried members of an international RCE support group for data on their experiences. The team designed a 24-question poll covering demographics, clinical data and therapies, then shared it with 1,856 participants of an online support group.⁵ 

Only 27% of RCE cases mentioned were seen by a corneal specialist, but 92% were referred to a healthcare professional of some sort. The predominant symptom was acute awakening pain (77%). RCE significantly impaired patients’ quality of life (68%). Some respondents believed that daily wear of a mask while COVID-19 mandates were in place may have increased the frequency of episodes (16%).

Regarding surgical procedures, manual debridement was the most performed (22%), effective in 30% of patients. Phototherapeutic keratectomy was performed in 20% of patients, effective in 60%. Almost 70% of patients were treated with hypertonic gel, which was the most efficient medical treatment, according to the patients (59%).

A dry eye patient cohort treated with rhNGF eye drops experienced significant symptom improvement. Researchers believe it could be a promising therapy. Photo: Chandra Mickles, OD. Click image to enlarge.

Ocular Surface

Several studies elaborated on risk factors and the efficacy of treatments for dry eye and related conditions.

• Meibomian gland (MG) atrophy factors. Upon evaluating MG morphology (atrophy and tortuosity) and risk factors in children ages four to 18, researchers found that high BMI, an unhealthy diet and reduced outdoor activity may induce abnormal changes.⁶

“MG abnormalities are not just found at high rates in older individuals but also show high prevalence in children,” Dr. Shovlin noted.

A total of 160 children at the Illinois Eye Institute were recruited. The team reported that the mean tear meniscus height was 0.23mm OD and 0.36mm OS. Mean noninvasive tear breakup time was 15.60 seconds OD and 15.96 seconds OS. No association was found between MG morphology and screen time.

“Eyecare practitioners should consider routine evaluation of the MGs in children during comprehensive eye exams, in addition to encouraging a healthy diet and time spent outside,” the study authors concluded in their abstract. 

• Finasteride risks. Long-term effects of the anti-androgenic hair loss medication should be considered before use in dry eye patients as it heightens meibomian gland dysfunction (MGD) risk, in addition to conjunctival and corneal abnormalities.⁷ Researchers noted that the androgen-sensitive meibomian glands may be altered in those taking anti-androgen medications, especially finasteride, given its unique potency and targeted effects compared with other anti-androgenics. 

The work included a retrospective chart review of 116 dry eye disease (DED) patients on finasteride (average age: 67.9, 95% male, 86% Caucasian). Analysis assessed clinical characteristics and Ocular Surface Disease Index (OSDI) scores among patients on varying doses of finasteride (23 patients were taking 1mg or 2.5mg, and 93 were taking 5mg).

Comparing exam findings during the initial and follow-up exams, the latter visit saw a significantly greater percentage of patients present with MGD and conjunctival and corneal abnormalities. Mean OSDI score was 24.4 and was slightly higher in patients taking 5mg of finasteride, though not statistically significant. Low-dose finasteride use was significantly associated with a greater frequency of cyclosporine use at the first and last exams. Otherwise, treatment modalities were no different between low- and high-dose groups.

“This study reinforces the importance of considering the long-term effects of finasteride use on DED as part of the systemic sequelae of androgen depletion and provides anticipatory guidance for patients and ophthalmologists,” the study authors concluded in their paper.

• Mediterranean diet and dry eye risk. Consuming high amounts of unsaturated fats and oils, such as a traditional Mediterranean diet, is generally considered healthy, but unfortunately this one may not necessarily help to reduce the risk of DED, according to one study. While otherwise considered healthy, this approach seemed to increase a patient’s risk for the condition. Those with strongest adherence to the diet’s basics had a greater risk of symptomatic DED.⁸

A total of 58,993 participants from the Dutch Lifelines population-based cohort were included in the study (60% female). The researchers administered the Women’s Health Study dry eye questionnaire to assess DED outcomes and quantified the level of adherence to a Mediterranean diet using a modified Trichopoulou’s Mediterranean diet score. They reported that 9.1% of participants had DED as defined by the Women’s Health Study and that greater adherence to a Mediterranean diet wasn’t associated with a decreased risk of dry eye.

Interestingly, they noted that higher Mediterranean diet score values (i.e., stronger adherence) were significantly associated with an increased risk of DED in all statistical models. Higher scores were also associated with a greater risk of symptomatic dry eye across all models after excluding participants with a DED diagnosis.

The researchers wrote in their abstract that the causes of this observed effect need further exploration.

• Growth factor drops improve dry eye. Neurosensory abnormalities have been increasingly recognized as a key feature of DED, so improving nerve health may be critical to restoring ocular homeostasis. Researchers recently found that recombinant human nerve growth factor (rhNGF) eye drops were well-tolerated in patients with moderate to severe dry eye as a promising therapy option.⁹ 

This randomized, vehicle-controlled Phase II study enrolled adult patients who had experienced moderate to severe dry eye for six months or longer. The researchers randomized the 261 participants into three treatment groups that received the following drops in both eyes for four weeks plus 12 weeks follow-up: 20µg/mL rhNGF TID, 20µg/mL rhNGF BID plus vehicle treatment once a day or vehicle TID. 

The mean change from baseline in Schirmer testing at week four was higher in the growth factor drops BID than the vehicle control arm (4.0mm vs. 1.7mm). Rates of response at week four were also higher in the TID (25.9%) and BID (29.3%) arms compared with the vehicle (11.9%) arm.

During follow-up, the TID arm had significantly greater Symptom Assessment in Dry Eye score reductions, indicating better symptom improvement, than the vehicle control arm at weeks eight, 12 and 16. More patients in the rhNGF drop arms than the vehicle arm reported one or more ocular adverse events in weeks one through four; the most common was eye pain. Mild eye pain was commonly reported but was generally transient and not reported after treatment discontinuation.

“Recombinant human growth factor addressing neurosensory abnormalities seems to help restore ocular homeostasis with only mild transient discomfort,” Dr. Shovlin says. “Clinicians may be able to rely upon this modality in the near future for the treatment of DED.”

• Gut microbiota and Sjögren’s. Gut health has important implications for the ocular surface, especially in Sjögren’s patients. Using metagenomic sequencing, researchers from Baylor College of Medicine were able to identify differential bacterial species from stool samples. Their confirmed that the Sjögren’s syndrome gut microbiome is less diverse and associated with increased ocular disease severity.¹⁰

The study included 20 healthy subjects as well as four patients with dry eye and seven with Sjögren’s syndrome (age-matched, all female). The researchers used the International Dry Eye Workshop guidelines to score ocular disease severity and prepared high-quality DNA for metagenomic sequencing and analysis from the collected stool samples.

The researchers reported significantly decreased organism diversity in Sjögren’s syndrome patients, a finding inversely correlated with ocular severity score. Interestingly, they found a significant difference between the healthy and Sjögren’s syndrome groups but not between the healthy and dry eye groups.

At the species level, Sjögren’s syndrome patients also had significantly less Bifidobacterium bifidum, a beneficial probiotic bacterial species commonly found in mammals, compared with healthy controls.

The researchers concluded that these species changes correlated with disease severity. Dr. Shovlin says he is hopeful that these findings can lead to future treatment approaches.

• Effects of glaucoma drops. Preservatives in topical glaucoma medications have long been known to cause ocular surface inflammation, but researchers suggested that not all preservatives do. They observed significant changes in the microbial composition of the ocular surfaces of patients using preserved glaucoma medications.

In the study, 17 patients (10 with unilateral glaucoma using preserved drops on just one eye and seven age-matched healthy controls with no history of ocular surface disease or eye drop use) had both eyes swabbed for V3-V4 16S rRNA sequencing. The researchers used air swabs as negative controls and compared the microbial diversity and composition of the swabs.

They found that samples from treated and untreated patient eyes had greater organism diversity and a distinct microbial composition compared with controls.¹¹ Eyes treated with preserved glaucoma drops had various gram-negative bacteria (mainly Akkermansia), which the researchers wrote in their abstract was significantly different from the mainly gram-positive microbes found in the healthy control eyes.

“These compositional differences were associated with decreased tear film measures and distinct inferred protein synthesis pathways, suggesting a potential link between microbial alterations and ocular surface inflammation,” the investigators concluded in their abstract.

Chalazion incision/excision was found to be more common among patients of male sex and those with rosacea. Photo: Joseph W. Sowka OD. Click image to enlarge.

Myopia

Multiple studies offered new findings on approaches to diagnosis and treatment.

• Initial myopic defocus. A relative peripheral hyperopia has been suggested as a myopia trigger in children. To better validate this finding, researchers measured high-resolution two-dimensional peripheral refraction maps during two years of myopia progression in a group of Chinese children. The team determined that relative refraction in the superior retina can be used as a predictor of central myopia.¹² 

After the study concluded, 214 children’s data (ages nine to 16) were available after one year and 152 children’s data were available after two. The peripheral refraction maps covered a field from nasal 30° to temporal 30° of every 1° and from superior 20° to inferior 16° of every 4°. The participants were classified into three refraction progression groups based on their refractive change in hyperopia, emmetropia and myopia.

After the first year, a refraction pattern significantly different from baseline was found in emmetropes. Baseline peripheral defocus in the central vertical field (horizontally, within ±15°) was found to be significantly correlated with central myopic shift, especially in the superior retina.

Linear regression revealed that emmetropic subjects with more myopic defocus in the superior retina had more myopic progression. The researchers found no obvious difference in baseline refraction pattern in the hyperopes and myopes. 

“This type of relative refraction in the superior retina could be used as a predictor of central myopia,” the team concluded in their abstract. “Devices for keeping the superior retina emmetropic in children might be a myopia control strategy.”

• Dexamethasone affects eye growth. A recent study suggests systemic use of dexamethasone interrupts emmetropization to slow myopia progression in children.¹³

The researchers administered dexamethasone or vehicle daily to chicks during the development of monocular form deprivation myopia (the last seven days of a 17-day period). Occluders were removed on the last day of treatment, and chicks experienced unrestricted vision for a recovery period of about 20 hours.

Data showed a significant decrease in choroidal IL6 gene expression in recovering eyes treated with dexamethasone vs. vehicle-treated chicks. The study authors detected no significant differences in IL6 gene expression in the choroids of control eyes between chicks treated with dexamethasone vs. vehicle.

“Dexamethasone treatment reduced choroidal gene expression of IL6 in recovering eyes, resulting in a disinhibition of scleral proteoglycan synthesis during recovery from induced myopia,” the study authors noted in their abstract. “These results provide additional support for a role of inflammation in visually regulated eye growth.”

Dr. Shovlin believes agents that reduce inflammation may someday help control myopia. “Unfortunately, systemic corticosteroids are not without their side effects, especially in a young population of users,” he notes. “Additional concerns should be focused on any viable option that may led to a significant increase in scleral proteoglycan synthesis in recovering eyes.”

• Posterior scleral strain. Imaging biomarkers (measuring deformability) may efficiently assess posterior eye wall strain for predicting risk for staphyloma formation.¹⁴

The study included 58 myopic eyes of 29 subjects (ages range: 37 to 87). To study the posterior shape and rigidity of each eye, researchers performed ultrasound B-mode scans in primary gaze across 100 frames. 

Relative stiffness of several regions of interest in the retina-choroid-sclera interface was measured across the 100 frames using strain elastography. Orbital fat was the baseline. At an interval of before-and-after compression, the researchers observed a significant difference between change in average relative stiffness for one region of interest and across two different regions of interest when compared with baseline.

The data showed that axial length and spherical error ranged from 22.59mm to 30.72mm and 0.7D to -15.7D, respectively. Also, the study authors reported that an increase in axial length (per 1mm) showed a decrease in average relative stiffness for a retina-choroid-sclera layer region of interest during compression of -0.283 as well as no compression of -0.0139. An increase of spherical error during compression revealed an increase in average relative stiffness of 0.00783 for a retina-choroid-sclera layer region of interest.

“Our qualitative and semiquantitative measure of posterior eye wall strain shows promise as an imaging biomarker identifying regions in myopic eyes that are less stiff and more susceptible to deformability that, when combined with other metrics (axial length, spherical error), may help assess at an early stage the risk of progression of a stable high myopia eye to pathologic myopia with staphyloma,” the study authors concluded in their abstract.

Chalazion

More information is needed to better understand the variables associated with chalazion diagnosis and surgical intervention. A recent study analyzed chalazion patients and healthy controls to identify common risk factors.¹⁵

A large United States claims database of 134,959 chalazion patients was compared 1:5 with matched controls (6,878,160). The researchers identified the variables correlated with diagnosis and surgical excision.

The data revealed that risk factors linked to chalazion diagnosis included female sex, non-white race, Northeast location and smoking. An increased risk was also associated with conditions that affect the periocular skin and tear film, such as blepharitis, MGD, rosacea and pterygium, as well as several non-ocular inflammatory conditions. These included gastritis, inflammatory bowel disease, sarcoidosis, seborrheic dermatitis and Grave’s disease. Conversely, diabetes and systemic sclerosis reduced the odds of diagnosis.

The likelihood of undergoing surgery for chalazion was increased among male patients as well as those with rosacea. Anxiety, diabetes, gastritis, seborrheic dermatitis, Sjögren’s syndrome and smoking decreased the odds of surgical intervention.

“This prompts further study of these variables and their relationship to chalazion diagnosis to understand physiology and improve clinical outcomes,” the authors concluded.

Ocular Infection

The newest Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) study data helps inform clinicians when choosing a therapy. Two analyses of the ongoing study found that this resistance remains prevalent. 

A nationwide surveillance study of in vitro antibacterial resistance levels among ocular pathogens, ARMOR is currently in its 13th year. As part of this trial, Staphylococcus aureus and coagulase-negative staphylococci (CoNS) from ocular infections were collected each year and sent to a laboratory to confirm the species.¹⁶

In one analysis, researchers examined longitudinal trends of the staphylococcal isolates collected, which included 2,847 S. aureus and 2,416 CoNS. Over the course of the 13-year collection period, data revealed that methicillin/oxacillin resistance decreased among both S. aureus and CoNS.¹⁶ The study authors also observed decreases in resistance for azithromycin, ciprofloxacin and tobramycin among S. aureus and for ciprofloxacin among CoNS. 

The researchers reported increases in resistance for chloramphenicol among S. aureus and for trimethoprim among CoNS. When examining the staphylococci collected in 2021 specifically, they found that more than 80% of methicillin-resistant isolates exhibited resistance to three or more antibiotic classes.¹⁶

Preliminary findings from an analysis of 446 isolates collected in 2021 were also presented. Among S. aureus, in vitro resistance was 53% to azithromycin, 37% to oxacillin/methicillin and 31% to ciprofloxacin. Among CoNS, in vitro resistance was 60% to azithromycin, 37% to oxacillin/methicillin, 20% to ciprofloxacin and 29% to trimethoprim.¹⁷

The data showed multi-drug resistance among 32% of S. aureus and 40% of CoNS isolates. Additionally, the rate of multi-drug resistance more than doubled in methicillin-resistant isolates. These initial findings revealed high rates of in vitro antibiotic resistance in ocular staphylococci collected in 2021 and are consistent with 2020 ARMOR data, according to the investigators.

“Analyses of antibiotic resistance among staphylococci collected over 13 years in ARMOR indicate that in vitro resistance has decreased only slightly over this timeframe for several antibiotics and is still prevalent in 2021,” the study authors wrote in their abstract.¹⁷ “Although the clinical relevance of in vitro data is unclear without consideration of the ocular pharmacokinetics of tested antibiotics, these findings warrant attention when choosing empiric therapy for the management of ocular staphylococcal infections.”

These informative findings will help ODs devise new ways to  help their patients. Check out ARVO’s full listing of abstracts and posters to see for yourself the latest advances in eye and vision care.

1. Wang C, Yue J, Niu Y, et al. Ocular antibiotics susceptibility of multidrug-resistant Staphylococcus isolated from ocular anterior segment. ARVO 2022 annual meeting. 2. Karamichos D, Escandon P, Nicholas S, et al. The surprising impact of hormones on keratoconus. ARVO 2022 annual meeting. 3. Shane J, Rigas Y, Shanks R, St. Leger A. Prob-eye-otics: cytokine producing therapeutic ocular commensals. ARVO 2022 annual meeting. 4. Quiroga-Garza M, Ortiz Morales, Bastán-Fabián D, et al. Prevalence of corneal endothelial pleomorphism, polymegethism and guttata in a Hispanic population. 2022 ARVO annual meeting. 5. Lama H, Bourges JL, Brézin A. Collecting data from a social network as a new method to explore recurrent corneal erosions syndrome. ARVO 2022 annual meeting. 6. Parikh M, Pang Y, Sicks L. Risk factors for meibomian gland morphology changes in children aged 4 to 18 years. ARVO 2022 annual meeting. 7. Nguyen B, Meer E, Gupta A, et al. The effect of finasteride on dry eye disease. ARVO 2022 annual meeting. 8. Magno M, Moschowits E, Beining M, et al. The relationship between adherence to a Mediterranean diet and dry eye disease. ARVO 2022 annual meeting. 9. Toyos M, Wirta D, Goosey J, et al. Phase II study of the efficacy and safety of recombinant human nerve growth factor (rhNGF) in patients with moderate-to-severe dry eye. ARVO 2022 annual meeting. 10. Schaefer L, Midani F, Trujillo-Vargas C, et la. Metagenomic sequencing of Sjögren syndrome and healthy gut microbiota reveals differential bacterial species that correlate with disease severity. ARVO 2022 annual meeting. 11. Chang C, Somohano K, Zemsky C, et al. Topical glaucoma therapy is associated with alterations of the ocular surface microbiome. ARVO 2022 annual meeting. 12. Lin Z, Lan W, Wen L, et al. Two-years evolution of two-dimensional peripheral refraction in children. ARVO 2022 annual meeting. 13. Summers J, Soriano D, Martinez E. Emmetropization is associated with a modified inflammatory response in the eye. ARVO 2022 annual meeting. 14. Lim SY, Ito K, Dan YS, et al. Assessment of stiffness of posterior eye wall in myopic eyes with an ultrasound-based algorithm using strain elastography. ARVO 2022 annual meeting. 15. Kim D, McGeehan B, Briceno C, et al. Demographic variables and systemic comorbidities associated with diagnosis of chalazion and chalazion incision/excision from a US claims database. ARVO 2022 annual meeting. 16. Asbell P, Sanfilippo C, DeCory H. Antibiotic resistance among ocular staphylococcal pathogens: longitudinal trends in the ARMOR study. ARVO 2022 annual meeting. 17. Sanfilippo C, DeCory H, Asbell P. Preliminary antibiotic resistance data among ocular bacterial pathogens in the ARMOR 2021 study. ARVO 2022 annual meeting.