March 22, 2023

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

  • Corneal crosslinking improved visual acuity after 15 years of follow up.
  • Nanodroppers may be an effective tool to achieve pupil dilation and cycloplegia while reducing medication waste.
  • A retrospective study found that acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is associated with risks for stroke or TIA.
  • Interferon-gamma release assay and the tuberculosis skin test in combination is more sensitive and specific for detecting ocular TB than either test alone.

Use it, don’t lose it: Efficacy of the Nanodropper


Would you use a bucket to fill a glass of water? While this may achieve your goal, it will also cause unnecessary waste. Similarly, administering standard 30-50mL eye drops may deliver drugs effectively yet inefficiently, given the eye’s ability to absorb only 7-10mL of fluid. To assess the role of eye drop volume in drug delivery, a study compared pupillary and refractive changes in a pediatric population following dilation with either 10.4mL drops using the Nanodropper adapter (n=50) or 50mL standard of care (SOC) drops (n=50). After dilation, maximum pupil diameter of the Nanodropper group was lower than the SOC group (mean: -0.01mm; 95%CI: -0.20mm, -0.03mm) , achieving noninferiority. However, post-dilation change in spherical equivalent (mean: 0.05D; 95%CI: -0.28D, 0.37D) and constriction percentage (mean: 0.57; 95%CI: -1.38, 2.51) in the Nanodropper group did not achieve noninferiority, though the differences between both groups were small and not clinically significant. These findings emphasize the comparable efficacy between small-volume eye drops and SOC drops for pupil dilation and cycloplegia, while showing their potential for decreasing medical waste and reducing systemic effects following absorption of certain drops.

Putting the breaks on keratoconus with corneal crosslinking

American Journal of Ophthalmology

‘Corneal collagen cross-linking’ might sound like a mouthful, but the results are eye-opening! Keratoconus is an insidiously progressive disease characterized by central and paracentral thinning of the cornea that results in a steep, conical cornea. Treatment modalities traditionally ranged from refractive correction in mild to moderate disease to corneal transplantation in more advanced stages. In 2016, corneal collagen cross-linking (CXL) was approved in the United States to reduce the progression of the disease. In this retrospective analysis, researchers studied 42 eyes that completed a 15-year follow-up from treatment of progressive keratoconus with CXL. Best-corrected visual acuity (BCVA), corneal topography, and corneal thickness were key indices tracked in this study. Compared to baseline, BCVA improved from 0.4 to 0.2 logMAR (95% CI: 0.03-0.23, P = 0.004), and the thinnest corneal thickness was reduced by 40µm (95% CI: 24-56, P < 0.001), though there were no significant changes in these parameters from 10 years to 15 years. There were also statistically significant improvements in maximum keratometry (95% CI: −3.5 to −9.6, P < 0.001), mean keratometry (95% CI: −1.8 to −4.1, P < 0.001), and corneal astigmatism (95% CI: −1.3 to −3.7, P < 0.001). While the results of the study may have been limited by the technological differences in measuring devices between initiation and completion, data supports CXL as a minimally-invasive and effective measure to deter the progression of keratoconus.

Physician authors of AAO guidelines fail to report financial conflicts of interests

JAMA Ophthalmology

Hold on to your wallets! A new study found that many physician authors of the American Association of Ophthalmology (AAO) guidelines had undisclosed financial ties to industry. The study reviewed clinical guidelines released by the AAO between 2016 and 2020. It was found that 59.6% of physician authors had received payments from industry while serving on the guideline committee, with a payment mean of $29,849.35 (SD: $54 131.56). Shockingly, among 149 physician authors who declared having no financial disclosures, over half (81; 54.4%) had payments reported by industry on the Open Payments database not disclosed within the guideline reports. Additionally, the study found that women physicians were paid significantly more than men for total payments (median [IQR] payments, $15 265 [$598.47-$41 104.67] vs. $301.48 [$218.85-$14 615.09]; difference, $14 963.52; P = .003). These findings suggest that there is a need for improved transparency and accuracy in disclosures of potential conflicts of interests among physician authors serving on guideline committees.

APMMPPE and the risks of stroke or TIA

British Journal of Ophthalmology

Can this rare chorioretinopathy lead to TIA and stroke? Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is a rare inflammatory chorioretinopathy that is typically self limited, affecting those 20-40 years of age. It presents with central scotomas, blurry vision, whitish-yellow placoid lesions on FFA and a flu-like prodrome with COVID-19, coxsackie virus, and other viruses as possible infectious agents. It is also associated with cerebral complications such as stroke and TIA, but only case reports or series are available. This multicentre retrospective review of 111 eyes (60 subjects) subjects from January 2009 to June 2020 determined the incidence of neurological complications and risk factors for stroke/TIA associated with APMPPE. APMMPPE was associated with stroke/TIA in 11.7% of subjects. At final follow-up, 6.3% had visual acuity of 6/15 or worse due to optic neuropathy and macular chorioretinal scars. Older age at presentation (OR 1.164, p=0.028) and previous history of APMPPE was associated with higher risk of vision loss (OR 63.367, OR 0.042). Collaborative care with ophthalmologists and neurologists, as well as new standard APMPPE treatment guidelines could ensure proper care for those affected by this uncommon disease.


Two tests are better than one in ocular tuberculosis

Ocular Immunology and Inflammation

Less may be more, but not when it comes to TB testing! Ocular tuberculosis (OTB) is a rare uveitic condition that can represent a diagnostic challenge due to its non-specific, variable presentations. Intraocular fluid sampling has poor sensitivity for identifying OTB, thus, clinical decisions must often rely on TB epidemiology, radiologic imaging, laboratory testing, and antitubercular treatment (ATT) response. Two commonly used biomarkers are interferon-gamma release assay (IGRA) and the tuberculosis skin test (TST), but while these tests are useful for identifying latent TB infections, their value in guiding the diagnosis of OTB is less established. In this prospective cohort study, 191 patients with any ocular inflammation suspicious for OTB underwent immunologic testing and those with highly suggestive findings, TST > 10mm, and/or IGRA > 0.35 IU/mL received ATT (n=72). Accuracy of diagnosis was then assessed by treatment response. Using TST and IGRA in combination as a screening tool for OTB had higher sensitivity (89.6%), specificity (99.2%), and area under the curve (0.98) compared to using TST or IGRA alone (p=0.01). Although adoption may be limited in real-world settings due to high cost and low accessibility of IGRA in developing countries, clinicians should consider using this combined approach in particularly ambiguous uveitis cases to guide therapeutic decision making.

Lens Landmarks

In a world before anti-VEGF, what could we do for wet AMD? Prior to the use of anti-VEGF injections, treatment options for wet AMD were very limited. The TAP study sought to evaluate the efficacy of Verteporfin Photodynamic Therapy (PDT) in reducing vision loss in patients with subfoveal choroidal neovascularization (CNV) caused by AMD. Across two studies, 609 patients were randomized to treatment with verteporfin (n= 402) and placebo (n= 207) followed by laser light at 689 nm delivering 50 J/cm2.

Key Points:
  • A greater proportion of verteporfin treated patients lost fewer than 15 letters of visual acuity at 12-month follow-up compared to the placebo group (61% versus 46%, P < 0.001)
  • In particular, patients with predominantly classic CNV lesions (>50% of the lesion) had the most notable reduction in vision loss, compared to those with 0-50%
Overall, the TAP trial is a landmark study that showed the efficacy and safety of PDT with verteporfin for treatment of CNV in classic wet AMD. And while this treatment is rarely used today due to the use of anti-VEGF medications that improve vision – not just slow vision loss – the TAP trial provided valuable information that impacted the practice of ophthalmology.

Question of the Week

A 65-year-old female with a history of smoking presents with a 3-month history of progressive, painless vision loss in her left eye. She denies any flashes, floaters, or eye redness. On examination, her visual acuity is 20/20 in the right eye and 20/100 in the left eye. Anterior segment examination is unremarkable, and there is no evidence of vitreous inflammation. Fundus examination of the left eye reveals a large, elevated, orange-yellow choroidal mass in the macular region with associated retinal detachment. There is no evidence of intraocular inflammation, subretinal fluid, or hemorrhage. B-scan ultrasonography confirms presence of the choroidal mass with high internal reflectivity.
What is the most likely diagnosis?

A. Choroidal melanoma
B. Choroidal metastasis
C. Choroidal hemangioma
D. Choroidal nevus

Keep scrolling for answer or click here

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Quiz Answer: B
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