April 12, 2023

The most important ophthalmology research updates, delivered directly to you.
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In this week's issue

  • Water-free cyclosporine solution (in perfluorobutylpentane) improves objective measures of dry eye disease as compared to vehicle alone.
  • Laser chorioretinal anastomosis in addition to anti-VEGF therapy may be useful in improving vision and decreasing need for injections in patients with CRVO.
  • Genotype-phenotype correlations are explored in patients with neuronal ceroid lipofuscinoses caused by specific CLN mutations.

Water-free cyclosporine for the management of dry eye

JAMA Ophthalmology

Few things are more inflammatory than living with dry eyes! Cyclosporine is an immunosuppressive compound that plays a key role in the management of dry eye disease. It is currently marketed as a topical aqueous emulsion due to the compound’s poor water solubility. Recently, clinical trials have been exploring the potential for water-free formulations using the solvent perfluorobutylpentane (F4H5). In the current phase 3 trial, a total of 834 participants used either cyclosporine or vehicle alone twice per day for 29 days. On a 15-point scale, total corneal fluorescein staining score improved by 4 grades in the cyclosporine group and 3.6 grade in the vehicle group (change [∆] = −0.4; 95% CI, −0.8 to 0; P = .03). Meanwhile, on a 100-point scale of dry eye symptoms, the cyclosporine group improved by 12.2 points and the vehicle group by 13.6 points (∆ = 1.4; 95% CI, −1.8 to 4.6; P = .38). These results show that water-free cyclosporine improves objective measures of dry eye disease as measured by fluorescein staining. The lack of significant symptomatic improvement may be attributed to the F4H5 vehicle’s established use for the treatment of dry eyes.

Can laser improve the treatment of central retinal vein occlusions?

American Journal of Ophthalmology

Blood and thunder meet their match! Central retinal vein occlusions (CRVOs) are currently treated with frequent anti-VEGF injections to help decrease the resultant macular edema. Laser chorioretinal anastomosis (L-CRA) in conjunction with anti-VEGF therapy is an attractive treatment option because, in addition to decreasing macular edema, it allows for bypass of the occluded vessel. This prospective, randomized clinical trial investigated 58 patients with CRVO who were treated with either L-CRA + ranibizumab (anti-VEGF) vs ranibizumab alone (1:1) 4 years out from the start of the study. At year 4, there was a significant increase in BCVA by 14.06 letters (p=0.009) in the L-CRA group, and a significant difference in annual mean injection requirements between the L-CRA group (0.25, 95% CI: [0.11, 0.56]) and the injection-only group (1.84, 95% CI: [1.34, 2.54]). This study highlights that the addition of L-CRA to ranibizumab therapy can be an effective treatment option to improve visual acuity and reduce the burden of intraocular injections in patients with CRVOs. Future studies can build upon these results by scaling up the number of participants and investigating the effectiveness of other bypass solutions.

Genotype-phenotype correlations in patients with CLN mutations causing Neuronal Ceroid Lipofuscinoses


Not all CLN genotype-phenotype relationships are created equal. Biallelic mutations in CLN genes cause neurodegenerative, lysosomal storage disorders known as neuronal ceroid lipofuscinoses (NCL). Classical symptoms of the disease include progressive and severe vision loss, cognitive decline, motor disorders, seizures, and premature death. However, symptoms may vary in onset and severity depending on the specific genetic mutation. This retrospective study identified five novel variants and four novel phenotypes of 11 patients diagnosed with NCL. Patients who were homozygous for large deletions in CLN3 developed systemic Batten disease, while patients who were heterozygous for the large deletion developed isolated retinal disease resembling retinitis pigmentosa. Understanding genotype-phenotype relationships allow medical teams to better explain prognosis which may impact life and family planning. Additionally, knowing if a certain genotype causes isolated retinal disease versus systemic neurologic degeneration can help determine if a patient is a good candidate for enrolling in the phase 1/2 gene therapy trial for CLN3 variants causing widespread disease.


Binocular amblyopia treatment improves manual dexterity


Help the eyes and the hands will follow! Amblyopia, a consequence of discordant binocular visual experience during the early period of visual development, is clinically defined by a visual acuity deficit in conjunction with an amblyogenic factor, most often strabismus or anisometropia. Amblyopia can potentially affect systems that rely on binocular vision for development, like the motor system. This study aimed to determine whether deficits in manual dexterity in children with amblyopia improve after binocular amblyopia treatment. 134 children with amblyopia were included, 75 in the "younger group" (aged 3 to <7 years), 59 in the "older group" (aged 7-10 years), and 40 age-similar controls. After 4-8 weeks of binocular amblyopia treatment, the manual dexterity scores of both treatment groups improved, though both groups remained significantly lower than controls (P = 0.03 and P = 0.01, respectively), with no significant difference in the younger vs older groups. Improvement in manual dexterity score was not associated with any baseline factors but was weakly correlated with the amount of visual acuity improvement (rs = 0.26; 95% CI, 0.09-0.41). Despite only using a single treatment approach (different from the gold standard), this study demonstrates that binocular amblyopia treatment improves visual acuity and manual dexterity.

Lens Landmarks

This UKPDS sought to answer a variety of questions related to the natural history and impact of hyperglycemia control for patients with Type II Diabetes. Such questions included what risk factors dictate the incidence and progression of diabetic retinopathy, in addition to what impact intensive glycemic control would yield on incidence and progression.

Key Points:
  • Risk factors for development and progression of diabetic retinopathy were noted to be higher blood glucose levels, high blood pressure, and interestingly, not smoking
  • The intensive glycemic control group had a lower A1c at study endpoints than the conventional diet-control group (7.0% versus 7.9%)
  • The intensive glycemic control group had lower likelihood of development of microvascular complications (need for PRP), but did have elevated risk of hypoglycemia
Overall, the UKPDS is a landmark study because it highlighted the important risk factors of high blood pressure and hyperglycemia in promoting the onset or progression of retinopathy in patients with Type II (non-insulin-dependent) diabetes mellitus. Furthermore, along with the DCCT (which studied Type I Diabetics), these studies helped to identify a new target for blood glucose control in Diabetic patients.

Question of the Week

A 3-month-old infant is brought to the ophthalmologist by parents due to a white appearance of the infant's pupils. The infant has a low birth weight, sensorineural hearing loss, congenital heart defects, and hepatosplenomegaly. Examination reveals bilateral cataracts with pearly white nuclear opacifications.
Which of the following characteristics is most indicative of congenital rubella syndrome (CRS) as the cause of the infant's clinical presentation?

A. The presence of elevated anti-rubella IgM antibodies in the infant's serum
B. Bilateral cataracts w/ pearly white nuclear opacifications containing live virus
C. The presence of concomitant congenital heart defects
D. The presence of concomitant hepatosplenomegaly 

Keep scrolling for answer or click here

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Quiz Answer: B
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