Comparing Treatments for Diabetic Retinopathy

By: Chista Niknam and Chirag Shah MD

Diabetic retinopathy (DR) is a common eye condition that affects people with diabetes, and it is a leading cause of blindness in adults. It occurs when high blood sugar levels damage the blood vessels in the retina, the light-sensitive layer at the back of the eye. The condition progresses in stages, from mild to severe, and can result in vision loss if left untreated.

All treatments are available at our clinic, and Dr. Shah evaluates each patient individually to determine the most appropriate therapy tailored to their unique situation. Click here to Book Online or Refer A Patient for diabetic eye examination and/or treatment.

Diabetic macular edema (DME) is a specific complication of DR that occurs when the damaged blood vessels in the retina leak fluid into the macula (the central part of the retina responsible for sharp, detailed vision). This fluid accumulation causes the macula to swell, leading to blurred or distorted central vision. While DR affects the entire retina, DME is primarily a result of fluid buildup in the macula, often causing more noticeable vision problems like difficulty reading or recognizing faces.

Treatment aims to reduce abnormal blood vessel growth, fluid leakage, and inflammation in the retina, helping to preserve vision. Below are common medical treatments and how they work:

1. Vabysmo (Faricimab)

Mechanism:

  • Vabysmo is a bispecific antibody that targets both VEGF-A (vascular endothelial growth factor) and Angiopoietin-2 (Ang-2), a protein involved in vascular leakage and inflammation. By blocking both, it helps stabilize blood vessels and reduce retinal swelling.

Visual Outcomes:

  • Vabysmo has shown significant improvements in visual acuity (sharpness of vision) in clinical trials for both DR and DME. Its dual-target approach (VEGF-A and Ang-2) helps reduce abnormal blood vessel growth and leakage, leading to better vision preservation.

Anatomical Outcomes:

  • Vabysmo reduces macular edema and central retinal thickness (CRT), which are common issues in DME. The drug’s dual mechanism provides long-lasting effects, meaning fewer injections are often required to achieve anatomical improvements.

2. Eylea (Aflibercept)

Mechanism:

  • Eylea is a recombinant fusion protein that blocks VEGF-A, VEGF-B, and Placental Growth Factor (PlGF). By targeting these factors, Eylea prevents abnormal blood vessel formation and leakage, which reduces swelling and preserves retinal health.

Visual Outcomes:

  • Eylea has demonstrated consistent improvements in visual acuity for patients with DME and DR. It is one of the most commonly used treatments due to its ability to stabilize or improve vision over time.

Anatomical Outcomes:

  • Eylea reduces macular edema and central retinal thickness (CRT) effectively. Patients experience significant decreases in retinal fluid and improvements in the retina’s structure, helping to stabilize vision.

3. Avastin (Bevacizumab)

Mechanism:

  • Avastin is a monoclonal antibody that targets VEGF-A, reducing the growth of abnormal blood vessels and preventing leakage in the retina. By inhibiting VEGF, it reduces vascular permeability and inflammation.

Visual Outcomes:

  • While not FDA-approved for ophthalmic use, Avastin is frequently used off-label for improving visual acuity in patients with DR and DME. It has shown significant benefits, though patients may require more frequent injections compared to Eylea or Vabysmo.

Anatomical Outcomes:

  • Avastin helps reduce retinal edema and decrease retinal thickness. However, since it is not specifically designed for eye use, it may need to be administered more often to maintain these anatomical improvements.

4. Ozurdex (Dexamethasone Intravitreal Implant)

Mechanism:

  • Ozurdex is a biodegradable intravitreal implant that releases dexamethasone, a corticosteroid that reduces inflammation and retinal edema. It works by inhibiting inflammatory mediators that contribute to fluid leakage in the retina.

Visual Outcomes:

  • Ozurdex is effective for patients who do not respond well to anti-VEGF treatments. It can lead to improvements in visual acuity by reducing inflammation and swelling. However, it may have a higher risk of side effects like cataracts and increased eye pressure with long-term use.

Anatomical Outcomes:

  • Ozurdex is particularly effective at reducing macular edema and improving the anatomical structure of the retina by inhibiting inflammatory cytokines. Its effect tends to last for several months, but the risks associated with steroid use (like increased intraocular pressure) must be considered.

5. Eylea HD (Aflibercept with Hydroxypropylmethylcellulose)

Mechanism:

  • Eylea HD is essentially a modified version of Eylea (aflibercept) combined with hydroxypropylmethylcellulose (HPMC). The addition of HPMC increases the viscosity of the drug, helping it remain in the eye longer and extending its therapeutic effect, while still blocking VEGF-A, VEGF-B, and PlGF.

Visual Outcomes:

  • Eylea HD has similar visual acuity improvements as regular Eylea but with the advantage of fewer injections due to its longer-lasting formulation. Its visual benefits are comparable to Eylea, as it targets VEGF-A, VEGF-B, and PlGF.

Anatomical Outcomes:

  • Eylea HD reduces macular edema and central retinal thickness like the original Eylea, with the potential advantage of requiring fewer injections due to the extended duration of action from its enhanced formulation.

To summarize, Anti-VEGF drugs, including Eylea, Vabysmo, and Avastin, work by blocking the action of VEGF, a protein responsible for abnormal blood vessel growth and fluid leakage in diabetic retinopathy. Eylea HD is a modified version of Eylea that offers the same anti-VEGF benefits but with a longer-lasting formulation, reducing the need for frequent injections. In contrast, steroids (like Ozurdex) reduce inflammation and fluid buildup but can increase the risk of eye pressure and cataracts with long-term use.

It’s important to note that while these treatments can significantly manage and improve the symptoms of diabetic retinopathy, they are not cures. They help control the disease, reduce swelling, stabilize vision, and prevent further damage, but ongoing monitoring and treatment may be necessary to maintain eye health over time.

Changes in CST after intravitreal anti-VEGF injection. (A) Before, and (B) after 1 month

OCT scans: before and one month after intravitreal Ozurdex 0.7 mg injection.

A Review of Faricimab Clinical Trials

macular degeneration targets faricimab aflibercept

Faricimab is a treatment for macular degeneration, specifically targeting Angiopoietins and the Tie-2 Pathway. Here we discuss a review of relevant clinical trials led by Dr. Arshad Khanani.

The review article PDF is available for download here, and below is a concise summary as well as additional, helpful resources related to Faricimab.

Summary:

Angiopoietins and Tie-2 Pathway: Initially, the review discusses angiopoietins (Ang-1 and Ang-2) and their interactions with the Tie-2 receptor. Ang-2 acts as a partial agonist or antagonist, and its inhibition consequently reduces vascular leakage and improves organ function.

Vascular and Extravascular Functions of Angiopoietin-2: In addition to the above, Ang-2 has functions in both vascular and extravascular settings for macular degeneration. Particularly in hyperglycemia and hypoxia, it plays a role in stimulating pericyte loss, neovascularization, and the breakdown of the Blood Retinal Barrier (BRB).

Diabetic Retinopathy and Macular Edema: Moreover, the article explores Ang-2’s role in macular degeneration, diabetic retinopathy and diabetic macular edema (DME). It emphasizes the importance of the retinal vasculature and the sensitivity of the retina to pericyte loss.

Angiopoietin-Like Proteins (ANGPTL) and Metabolism: Additionally, the paper delves into ANGPTL, which are similar to angiopoietins but have distinct roles in glucose and lipid metabolism. Specifically, ANGPTL-3, ANGPTL-4, and ANGPTL-8 are discussed in this context.

Treatment and Therapeutic Targets: The document also mentions various treatments and innovative therapies for neovascular age-related macular degeneration and diabetic retinopathy, including surgical innovations.

Review:

The systematic review article provides a comprehensive analysis of angiopoietins and their role in macular degeneration, vascular biology, inflammation, and metabolic processes. Notably, the focus on diabetic retinopathy and the connection between angiopoietins and metabolic disorders adds significant value.

The paper’s strength lies in its integration of various studies and research findings, thereby providing a holistic view. Furthermore, the exploration of ANGPTL and their role in metabolic processes is particularly intriguing and opens avenues for further research.

However, the study might be challenging for a lay reader due to its technical language and complex concepts. Therefore, its target audiences are medical professionals or researchers in the field of biology, medicine, or related disciplines.

Overall, this review article is a valuable resource for those interested in the intricate interplay between angiopoietins, vascular biology, and metabolic disorders. Consequently, it offers insights that could potentially lead to new therapeutic approaches for conditions like diabetic retinopathy and metabolic syndromes.

https://www.retinalphysician.com/issues/2019/march-2019/the-mechanism-of-the-bispecific-antibody-faricimab

https://www.gene.com/download/pdf/Vabysmo_Product_FactSheet_4.13.23.pdf

http://www.retinapodcast.com/episodes/2019/3/5/episode-157-march-retinal-physician-review-with-dr-shriji-patel-including-discussion-of-complement-inhibition-for-amd-faricimab-brolucizimab-and-prefilled-syringes-for-injectable-medications?rq=faricimab

Breaking Ground in Macular Degeneration Treatment: Dr. Shah’s Clinic Leads the Way with New Medications

Introduction

Macular degeneration is a prevalent eye condition that affects millions of people worldwide, leading to vision loss and decreased quality of life. In the quest for more effective treatments, medical research has made significant strides in developing new medications to combat this debilitating disease. At the forefront of these advancements is Dr. Shah’s clinic, where cutting-edge treatments for macular degeneration are being offered. Dr. Shah is not only a leading expert in the field but also actively involved in clinical trials, bringing hope and potential relief to countless patients.

The Need for New Medications

Macular degeneration is typically divided into two main types: dry and wet. The dry form, while more common, lacks definitive treatment options. This has driven researchers and medical professionals to focus their efforts on the wet form, characterized by abnormal blood vessel growth in the retina. Conventional treatment for wet macular degeneration involves regular intravitreal injections of anti-VEGF medications. However, not all patients respond equally to this treatment, and its frequent administration can be burdensome.

New Medications on the Horizon

  1. Targeted Complement Inhibitors: Researchers have identified that dysregulation of the complement system plays a significant role in wet AMD development. By inhibiting specific components of this system, targeted complement inhibitors offer a novel approach to managing the disease. These medications have shown promising results in clinical trials, demonstrating their potential to provide more personalized and effective treatment for patients.
  2. Tyrosine Kinase (TK) Inhibitors: TK is another protein involved in the abnormal blood vessel growth seen in wet AMD. TK inhibitors have emerged as potential adjunctive therapies to anti-VEGF medications. Clinical trials have shown that combining TK inhibitors with anti-VEGF treatments can lead to improved outcomes, potentially reducing the frequency of injections and enhancing patient satisfaction.

Dr. Shah’s Contributions to Advancements

As a distinguished ophthalmologist specializing in retinal diseases, Dr. Shah has been at the forefront of introducing new medications for macular degeneration in his clinic. His commitment to staying current with the latest research and advancements has led him to actively participate in clinical trials. By participating in these trials, Dr. Shah is not only offering his patients access to cutting-edge treatments but also contributing to the advancement of medical knowledge and the potential for better outcomes for all patients with macular degeneration.

The Importance of Clinical Trials

Clinical trials are a crucial aspect of medical research and innovation. Through these trials, new medications undergo rigorous testing to determine their safety and effectiveness. By being part of clinical trials, Dr. Shah is playing a vital role in shaping the future of macular degeneration treatment. Patients who choose to participate in these trials not only have access to potential breakthrough therapies but also contribute to the collective knowledge that will ultimately benefit countless others facing macular degeneration.

Conclusion

Macular degeneration is a sight-threatening condition that demands constant exploration and innovation in treatment options. With new medications on the horizon, patients have reason to be hopeful. Dr. Shah’s clinic stands at the forefront of these developments, offering cutting-edge treatments and actively participating in clinical trials to bring advancements from the research lab to the patient’s bedside. As we look forward to a brighter future for macular degeneration patients, it is reassuring to know that dedicated professionals like Dr. Shah are working tirelessly to improve outcomes and quality of life for those affected by this challenging condition. If you or a loved one is struggling with macular degeneration, consider consulting with Dr. Shah to explore the latest treatment options and potential participation in clinical trials for a chance at a better tomorrow.