Retinitis pigmentosa (RP) is a hereditary retinal dystrophy mainly of the rod photoreceptors.¹ The pathogenesis of RP is multifactorial and includes light damage, apoptosis, endoplasmic reticulum stress, and ciliary transport dysfunction, finally culminating in the death of rod photoreceptors.² This rod loss eventually affects the retinal pigment epithelium (RPE) and cone photoreceptors. This sequence explains why patients who suffer from RP experience a loss of dim vision, termed night blindness, as well as a gradual decrease of peripheral vision and disturbance of color perception.¹

RP is associated with other causes of low vision, including posterior subcapsular cataract, refractive errors, keratoconus, and cystoid macular edema (CME).³ CME complicates the visual deterioration of RP through an increase in photoreceptor death.⁴ 

Treatment for CME secondary to RP has included oral carbonic anhydrase inhibitors, oral minocycline, intravitreal anti–vascular endothelial growth factor (VEGF) injection, intravitreal steroids, vitrectomy with inner limiting membrane peeling and gas tamponade, as well as subliminal micropulse yellow laser therapy.⁵ However, a thorough study into the resolution of CME with vitamins has not yet been conducted.

We present a case of a patient with CME secondary to RP who showed improvement in her edema after starting to use nutritional supplements.

Case Presentation

The patient is a 28-year-old female who has been suffering from bilateral CME secondary to RP, as well as bilateral epiretinal membranes. She also had a floater in the right eye (Figure 1). Her RP had been diagnosed when she was 2 years old and her CME had been stable for the

previous 8 years. Her electroretinograms (ERGs) in the past showed very mild cone flicker response but essentially a flat response bilaterally and she had discontinued taking brinzolamide ophthalmic suspension (Azopt; Alcon), acetazolamide (Diamox; Teva Pharmaceuticals), and vitamin A many visits prior due to lack of improvement. She also had a history of hypothyroidism, which was treated with levothyroxine. Genetic testing showed that she was RHO dominant. Her visual acuity was 20/40 bilaterally, but her visual fields were largely constricted on Humphrey visual field 30-2. Her intraocular pressure was 16 in the right eye and 18 in the left eye. 

The patient was undergoing fertility treatments and began taking prenatal vitamins in March 2024. Her prenatal regimen included N-acetyl cysteine (NAC) 1000 mg/day, vitamin D₃ 2000 IU/day, coenzyme Q10 (CoQ10) 600 mg/day, and other vitamins. (The complete nutritional supplementation regimen is detailed in Table 1).  

When she came for her next visit, in April 2024, her CME had improved bilaterally, with a 61 µm decrease (13.5%) in the thickness of the CME on the right eye and a 47 µm decrease (11.6%) in the thickness of the CME on the left eye since her prior visit in October 2023 (Figure 2, A and B). Prior to vitamin supplementation, visits in 2021 and 2022 did not show similar improvement in CME thickness (Figure 3, A and B).

Discussion

Earlier studies suggested that high doses of vitamin A (around 15,000 IU/day) might slow down the rate of vision loss in adults with RP.⁶ However, there was no reported correlation between vitamin A intake and CME development or resolution.⁷ Although iodine was postulated to be associated with a better outcome for RP,⁷ the most studied beneficial supplements for RP include vitamin A, lutein, and Omega-3s, particularly docosahexaenoic acid (DHA).⁸ 

Studies have shown that vitamin E can actually worsen the condition.⁹ Vitamin E is present in AREDS2 supplements used for age-related macular degeneration, so caution must be exercised when prescribing these supplements to a patient with CME. Vitamin B hasn’t been a major area of investigation regarding CME, despite a prior case report showing that a low dose of niacin (vitamin B₃) induced CME which resolved after discontinuing the supplement.¹⁰ This harmful effect has been consistently described in the literature elsewhere.⁶

Vitamin C, L-Carnitine, and selenium are antioxidants, which can help combat oxidative stress in the body. It’s theorized that oxidative stress is how RP can damage the retinal cells. However there’s currently no strong scientific evidence that supplementation of these vitamins directly slows down RP progression or improves vision in RP patients.¹¹ Likewise, there have been no studies examining the relationships between RP and biotin, chromium (a blood sugar regulator), folate (a crucial player in DNA synthesis, cell division, and amino acid metabolism), magnesium (a co-factor in many biochemical reactions in the body), copper, choline, or molybdenum. Similarly, there are no direct human studies examining the relationship between vitamin D and RP, despite the protective effect of vitamin D on RPE cells being demonstrated in vitro.¹²

Research suggests that high levels of calcium inside photoreceptor cells can be detrimental and contribute to RP progression. When excessive calcium enters these cells, it can activate enzymes that damage the cells and lead to cell death. This ultimately contributes to vision loss in RP patients. Some studies have explored the use of calcium channel blockers—medications that prevent calcium from entering cells—as a potential therapeutic approach for RP. However, the effectiveness of this approach in humans with RP is still under investigation.¹³ Similarly, studies suggest that iron accumulation in the retina might be a contributing factor in RP development or progression. This iron overload can cause oxidative stress, which damages retinal cells, including photoreceptors responsible for vision.¹⁴ 

NAC showed promise as a potential treatment for RP. NAC is a potent antioxidant that helps combat oxidative stress in the body, which is thought to be a major contributor to photoreceptor cell death in RP. NAC can slow down photoreceptor degeneration and improve retinal function.¹⁵ Prompted by these positive results, initial clinical trials in humans with RP have yielded encouraging findings. A phase 1 trial showed that NAC was well-tolerated and resulted in improvements in visual function, including light sensitivity and macular cone function.¹⁶

While the phase 1 trial of NAC in RP is a positive step, it was a small-scale study. More extensive clinical trials are needed to confirm the effectiveness of NAC in a larger population of RP patients. A larger phase 3 clinical trial, called NAC Attack, is currently underway to test the efficacy of NAC in slowing or stopping vision loss in RP patients.¹⁷

There is also a promising connection between CoQ10 and RP. CoQ10 is an antioxidant that plays a vital role in cellular energy production and counteracting oxidative stress, as well as assisting with mitochondrial functions throughout the body, including in retinal cells. A recent study identified specific CoQ10 biosynthesis pathway gene defects as a cause of RP in some cases, highlighting a potential role for CoQ10 deficiency in the disease.¹⁸

Zinc is a trace mineral vital for various bodily functions, and it plays a critical role in eye health. It is essential for protein synthesis and stabilizing cell membranes in the retina, particularly in photoreceptor cells responsible for vision. Furthermore, zinc is a key component of rhodopsin, a light-sensitive protein in photoreceptor cells. Deficiency might impair rhodopsin function and vision.¹⁹ 

Conclusion

Our presented case demonstrated a remarkable reduction in the severity of CME after starting nutritional supplements, most notably NAC, which is currently being actively studied in the treatment of RP. Our case suggests favorable results for the current trials underway. NRP

Amr K. Hassan, MD, MSc, is a retina fellow in the department of ophthalmology at the Gavin Herbert Eye Institute of the University of California in Irvine, California. He reports no disclosures. Reach Dr. Hassan at dramrhassan@yahoo.com.

Mitul Mehta, MD, MS, FASRS, is an ophthalmologist who specializes in medical and surgical diseases of the retina, and an assistant professor at the Gavin Herbert Eye Institute. He reports no disclosures.

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