When used together with an antiviral such as acyclovir, corticosteroid treatments could be more effective for herpes stromal keratitis compared with monotherapy of an antiviral or corticosteroid, researchers say.

Among classifications of herpes simplex keratitis, herpes stromal keratitis is a leading cause of irreversible corneal scarring, thinning, neovascularization and infectious blindness worldwide. Disease outcomes including vision loss, neovascularization and angiogenesis may progressively worsen after each recurrence. The standard treatment for herpes stromal keratitis includes antiviral medications in combination with corticosteroids, which addresses both the viral and immunomodulatory pathogenicity of the condition by reducing inflammation and inhibiting herpes simplex virus replication in the corneal stroma. Researchers recently conducted a systematic review to identify and compare interventions for treating herpes stromal keratitis and patient outcomes. They found that corticosteroids and antivirals managed the condition most effectively only when used concurrently. Results fared better than using either as monotherapy.

Two independent reviewers screened 168 records and used seven papers for data extraction. The research team examined both the conventional treatment with corticosteroids and antivirals and potential alternatives such as flurbiprofen, cyclosporine A and tacrolimus by their treatment success rate, best-corrected visual acuity, resolution time of successful treatment, time to failure, IOP and adverse events.

Patients with herpes stromal keratitis who received prednisolone phosphate and acyclovir showed a higher treatment success rate and significantly longer time to failure compared with patients receiving only acyclovir. No difference in resolution time was found between oral and topical acyclovir. Between groups receiving dexamethasone and flurbiprofen, resolution occurred in 93 percent and 67 percent of patients and BCVA (logMAR) improved from 1.0 to 0.30 and 0.48, respectively. BCVA improved in both cyclosporine A and its control (prednisolone) groups. A tacrolimus treatment group showed greater improvement in best-corrected visual acuity compared with its control (prednisolone) group.

“These interventions could be potential novel approaches to the management of herpes stromal keratitis and allow health practitioners and patients—especially those who are unsuccessful with the standard treatment—to have access to alternative treatment plans that could be equally effective and potentially safer with fewer side effects,” the researchers wrote in their paper in Ophthalmic Epidemiology.

 

Ophthalmic Epidemiol. May 15, 2023. [Epub ahead of print].

Li X, Nayeni M, Malvankar-Mehta MS. 

 

Calcium Channel Blockers Linked to Glaucoma

A recent meta-analysis published in Ophthalmology examined associations of four categories of systemic medications—antihypertensives, lipid-lowering drugs, antidepressants and antidiabetic agents—with glaucoma prevalence and IOP in 11 population-based cohort studies of the European Eye Epidemiology consortium. The team found significant associations between use of calcium channel blockers, one class of antihypertensive studied, and increased glaucoma prevalence. However, nonselective and selective beta-blockers were associated with lower IOP. Use of other antihypertensive medications, lipid-lowering medications, antidepressants or antidiabetic medications was not associated with glaucoma prevalence or lower IOP.

A total of 143,240 participants were included in the glaucoma analyses and 47,177 participants in the IOP analyses. Antihypertensive drugs assessed included beta-blockers, diuretics, calcium channel blockers, alpha-agonists, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Associations with antidiabetic medications were examined in diabetic participants only.

In the meta-analyses, use of calcium channel blockers was associated with a higher prevalence of glaucoma (odds ratio [OR]: 1.23). This association was stronger for monotherapy of calcium channel blockers with direct cardiac effects (OR: 1.96). Use of systemic beta-blockers was associated with a lower IOP (-0.33 mmHg). Monotherapy of both selective (-0.45 mmHg) and nonselective (-0.54 mmHg) systemic beta-blockers was associated with lower IOP. There was a suggestive association between use of high-ceiling diuretics and lower IOP (-0.30 mmHg) but not when used as monotherapy.

“It is possible that systemic beta-blockers do not reduce the risk of glaucoma per se, but limit the detection of glaucoma given that elevated IOP is often a trigger for diagnosing glaucoma,” the authors noted in their paper. “The blood pressure-lowering effect of systemic beta-blockers may thus balance out the IOP-lowering effect on glaucoma risk, explaining the null association between use of systemic beta-blockers and glaucoma prevalence.”

The researchers also found that nocturnal systemic hypotension may be associated with increased risk of glaucoma progression. “This may thus explain the association between calcium channel blockers and increased glaucoma prevalence, if calcium channel blockers are preferentially taken at bedtime,” they proposed.

Because time of medication use was not known in the studies examined, they were not able to provide evidence for this hypothesis.

“A potentially harmful association of calcium channel blockers for glaucoma is particularly noteworthy, as this is a commonly prescribed class of medication,” the researchers concluded in their paper. “If further studies confirm a causal nature for this association, this may inform alternative treatment strategies for hypertensive patients with, or at risk of, glaucoma.”

 

Ophthalmology. May 5, 2023. [Epub ahead of print].

Vergroesen JE, Schuster AK, Stuart KV, et al.

 

Minimizing Systematic Bias in IOL Power Calculations

Scientists developed a simplified method to optimize lens constants to zero the Mean Prediction Error of an intraocular calculation formula, without the need to program the formula itself, by exploring the influence of IOL and corneal power on the refractive impact of variations in effective lens position.

They looked at retrospective data from 8,878 patients with cataracts with pre- and postoperative measurements available using four IOL models and six IOL power calculation formulas.

The scientists used a schematic eye model to study the impact of small variations in effective lens position on the postoperative spherical equivalent refraction. They investigated the impact of keratometry and IOL power (P) on SE and used a theoretical thick lens model to devise a formula to zero the average prediction error of an IOL power calculation formula. This was achieved by incrementing the predicted effective lens position, which could then be translated into an increment in the intraocular lens  constant. This method was tested on documented real-life postoperative datasets, using different intraocular lens models and single-constant optimized IOL calculation formulas.

Here are some of the findings from the paper:

  • For small variations in ELP, an exponential relationship was found between IOL power and the resultant postoperative refractive variation. 
  • The ELP adjustment necessary to zero the mean prediction error equated to a ratio between the mean prediction error and the mean of the following expression: 0.0006*(P²+2K*P) on the considered datasets. 
  • The accuracy of the values obtained using this formula was confirmed on documented postoperative datasets, and on published and non-published lens-calculation formulas.

Scientists concluded that the proposed method would enable surgeons without special expertise to optimize an intraocular lens constant to nullify the mean prediction error on a documented dataset without coding the different formulas. They added that the influence of individual eyes was proportional to the squared power of the implanted intraocular lens.

 

Am J Ophthalmol 2023; May 5. [Epub ahead of print].

Gatinel D, Debellemanière G, Saad A, et al. 

 

Diabetes and Fuchs’ Endothelial Corneal Dystrophy

New data showed that female sex, European ancestry and multimorbidity are associated with an increased risk of Fuchs’ endothelial corneal dystrophy. These findings, which were recently published in Cornea, also highlight a relationship between diabetes and Fuchs’ dystrophy.

The researchers, who aimed to assess risk for demographic variables and other health conditions associated with FECD, developed a case-control algorithm based on structured electronic health record data. Accuracy of the algorithm was confirmed by reviewing charts at three Veterans Affairs Medical Centers.

In this analysis, the algorithm was applied to the Department of Veterans Affairs Million Veteran Program cohort. Sex, genetic ancestry, comorbidities, diagnostic phecodes and laboratory values were extracted for these individuals. In their report, the investigators determined the association of these risk factors with a Fuchs’ endothelial dystrophy diagnosis via single-variable and multiple-variable logistic regression models.

Data showed that female sex, European genetic ancestry and a greater number of comorbidities is associated with an increased risk of Fuchs’ dystrophy. Of 1,417 diagnostic phecodes evaluated, the study authors reported that 15 percent (n=213) had a significant association with Fuchs’. This encompassed ocular and nonocular conditions, including diabetes.

Five of 69 laboratory values (7.2 percent) were associated with Fuchs. The connection between diabetes and an increased FECD risk was supported by endocrine/metabolic clinic encounter codes and altered patterns of laboratory values.

“In the future, it will be important to better understand the relationship between Fuchs’ dystrophy and diabetes mellitus. Insights regarding this relationship may identify opportunities for slowing Fuchs’ progression,” the study authors noted in their paper. “We anticipate that our case-control algorithm will open the door for further Fuchs’ endothelial corneal dystrophy gene discovery.”

 

Cornea. May 12, 2023. [Epub ahead of print].

Nealon CL, Halladay CW, Gorman BR, et al.