Current Issue

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In this week’s issue

• A dexamethasone intracanalicular insert may provide a dropless treatment alternative for dry eye.
• MYL-1701P, a biosimilar to aflibercept, had similar efficacy, safety and immunogenicity in diabetic macular edema.
• Psoriasis was found to be an independent risk factor for developing neovascular AMD in diabetic patients.
• While IV methylprednisolone led to greater decreases of TSH antibody in the first 3 months, levels did not differ from no treatment controls at 12 months.
• A new study explores two-year efficacy & safety profiles of different anti-VEGF regimens for neovascular age-related macular degeneration.

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Ophthalmology

Dexamethasone intracanalicular insert for treatment of dry eye

An option to ditch the drops for dry eye? Dry eye is a common condition affecting millions of patients in the U.S. The pathophysiology of dry eye is linked to inflammation, and topical corticosteroids are often used in treatment. Nevertheless, issues such as discomfort, forgetting to use drops, and difficulty instilling the drops have raised interest in a dropless alternative. In this single-center, double-masked, randomized controlled trial, researchers evaluated the safety and efficacy of a commercially available dexamethasone intracanalicular insert (Dextenza, Ocular Therapeutix) for the management of clinically significant aqueous-deficient dry eye. Participants (n=75) were randomized such that one eye received the insert while the other eye received a sham collagen plug. While both groups had similar dry eye severity at baseline, the dexamethasone group showed significantly less corneal fluorescein staining at week 4 (mean difference [MD], -0.55; 95% confidence interval [CI], -0.91 to -0.19), and less conjunctival lissamine staining at weeks 4 (MD, -0.68; 95% CI, -1.05 to -0.30) and 6 (MD, -0.34; 95% CI, -0.65 to -0.02). The dexamethasone group had a higher rate of intraocular pressure elevation by 5-10 mmHg from baseline (relative risk, 9.00; 95% CI, 1.14 to 71.0). These results suggest that the insert may function via both anti-inflammatory and physically occlusive mechanisms to improve dry eye symptoms, offering a new possible use for this device that is currently FDA-approved only for intraocular inflammation and post-cataract ophthalmic pain.

JAMA Ophthalmology

Insight into the INSIGHT randomized control trial

Sounds very biosimilar to me…The biologic aflibercept, an injectable recombinant protein that binds vascular endothelial growth factor (VEGF) has been approved for neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), macular edema secondary to retinal vein occlusion, diabetic retinopathy, and retinopathy of prematurity. While an aflibercept biosimilar has already demonstrated equivalence in treating neovascular AMD, FDA approval of its use in DME has only been indicated via extrapolation. In this multicenter, randomized, double-masked, active-controlled INSIGHT study, researchers evaluated the safety and efficacy of the aflibercept biosimilar (MYL-1701P) compared to the original biologic in treating DME. Of 355 participants randomized between the two groups, the biosimilar MYL-1701P demonstrated equivalent outcomes to aflibercept over 52 weeks in terms of treatment-emergent adverse events, number of injections, pharmacokinetics, and change in best corrected visual acuity. This data suggests that the aflibercept biosimilar (MYL-1701P) is an acceptable alternative to the biologic aflibercept, providing comparable efficacy and safety in the treatment of DME.

American Journal of Ophthalmology

Association between psoriasis & neovascular AMD in diabetes

Skin checks at the eye doctor’s office? Psoriasis might be the reason you start. Psoriasis is a common autoimmune disease characterized by scaly, salmon-pink skin plaques that can also present with ocular complications such as dry eye disease, uveitis, and conjunctivitis. Epidemiologic studies also suggest a link between psoriasis and retinal vein occlusion, likely due to shared risk factors such as hypertension, diabetes mellitus (DM), and cardiovascular complications. One key mechanism in psoriasis involves the stimulation of angiogenesis by vascular endothelial growth factor (VEGF), suggesting a potential association with neovascular age-related macular degeneration (nAMD). This retrospective study used a population-based cohort of over 2.2 million Korean individuals aged 40 and over with type 2 DM to explore the relationship between nAMD and psoriasis. Patients were divided into a psoriasis group (n= 20,853) and a control group (n= 2,224,505). The psoriasis group had higher rates of cigarette smoking, hypertension, dyslipidemia, chronic kidney disease, and diabetic retinopathy compared to diabetic patients without psoriasis. After adjusting for factors such as age, sex, BMI, smoking, alcohol consumption, and other health conditions, the psoriasis group showed a significantly higher risk of developing nAMD with a hazard ratio of 1.279 (95% CI, 1.052-1.551). Although the study’s population limits its broader generalizability, the findings highlight the importance of careful monitoring for the development of nAMD diabetic patients, especially those with psoriasis.

British Journal of Ophthalmology

Effect of methylprednisolone on TSH antibodies in thyroid eye disease

Do you have exophthalmos yet for this fascinating study? While it’s well known that methylprednisolone, a corticosteroid, can reduce extraocular muscle swelling and relieve pressure on the optic nerve in patients with thyroid eye disease, less is understood about its specific impact on TSH antibody levels. In a retrospective, observational study, researchers enrolled 163 participants with moderate-to-severe thyroid eye disease for 12 months to investigate how intravenous methylprednisolone (IVMP) affects TSH antibody levels. Patients were divided into a treatment group and a control group, and prognostic factors for treatment response were analyzed using multivariable logistic regression. Participants treated with IVMP experienced a more rapid decrease in TSH antibody titers during the first six months, but later matched the control group for total titer levels. Additionally, total cholesterol was identified as a significant prognostic factor for steroid response (Odds Ratio, 1.0217), indicating that individuals with higher cholesterol levels may respond less effectively to the treatment. Overall, the study suggests that while methylprednisolone can accelerate the reduction of TSH antibodies in the short term, the long-term levels out by 12 months, with cholesterol potentially influencing the treatment’s efficacy. 

Eye

Which anti-VEGF regimen reigns supreme for treating nAMD?

Eeny, meeny, miny, moe, which anti-VEGF regimen is the way to go? Age-related macular degeneration (AMD) is a major cause of vision impairment in the elderly, with neovascular AMD (nAMD) responsible for the most severe cases. This network meta-analysis sought to compare the efficacy and safety of various anti-VEGF regimens over a two year period, addressing a gap in previous studies that largely focused on one-year outcomes. The study systematically reviewed 19 trials and included 12,654 patients. The analysis found that ranibizumab 0.5 mg administered biweekly using a treat and extend (T&E) regimen led to superior vision gain and ranked among the best regimens for improving best-corrected visual acuity. In contrast, brolucizumab 6 mg (3 + Q12W/ Q8W) (RR = 6.04, 95% CI: 1.30–28.02) and the port delivery system (PDS) 100 mg/ml (Q24W) (RR = 10.95, 95% CI: 2.14–56.02) were associated with higher risks of serious ocular adverse events compared to sham therapy. Based on the findings, ranibizumab 0.5 mg (2-week T&E) appears to be the optimal anti-VEGF therapy for nAMD over a two-year period, effectively balancing efficacy and safety. However, further investigation is needed to comprehensively evaluate long-term outcomes and account for potential confounding variables.

Ophthalmology Retina

Interim results of phase III port delivery system of ranibizumab for nAMD

Will this port delivery system change monthly needle sticks into an easy bi-annual oil change? The Port Delivery System (PDS) with ranibizumab (Lucentis) is approved for neovascular age-related macular degeneration (nAMD) and is being evaluated for long-term safety in the Portal trial, following patients who were previously in the phase II Ladder or phase III Archway studies. PDS has some perceived advantages over traditional anti-VEGF injections, including reduced treatment burden, sustained drug delivery, patient preference, and high adherence. The implant sits in the sclera near the pars plana and dispenses drugs into the vitreous cavity. The aim of this phase III trial is to assess the durability of visual and anatomical outcomes with the PDS and its safety over time. This study compares PDS refill-exchanges every 24 weeks (Q24W) versus patients in the Ladder and Archway studies receiving monthly ranibizumab injections. Results show that 24.7% of the PDS population had at least one ocular adverse event, with cataracts (11%) and vitreous hemorrhage (6%) being the most common. Visual acuity remained stable over 48 months, and 95% of patients did not require supplemental treatment before refill-exchanges. Among patients previously receiving monthly ranibizumab, 92% preferred the PDS over injections. In conclusion, PDS 100 mg/ml maintains visual and anatomical outcomes over four years and is generally preferred over monthly injections, with a well-characterized safety profile.

Treatment of AMD with Phototherapy (TAP) - 1999

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.

A 68-year-old woman presents to your clinic for a cataract evaluation. Her past medical history includes supraventricular tachycardia and inflammatory arthritis. Her current medications include prednisone, methotrexate, estradiol, diltiazem, and Restasis. Her BCVA is 20/40 OD and 20/50 OS. Your slit lamp exam of the external and anterior segment structures is all WNL except for 2+ NS OU. The dilated fundus exam reveals mild bilateral paracentral RPE depigmentation with foveal sparing. You document your finding with fundus photography and decide to refer the patient to one of your retina colleagues before proceeding with cataract surgery.

Based on the history and exam findings for this patient, which of the following tests or additional pieces of information would be MOST helpful to support your suspicions about the cause of the retinal pathology?

A. Amsler grid test

B. History of past infections

C. Color vision testing

D. List of discontinued medications

Click Here For Answers!