Krill’s Disease

Krill’s disease, commonly known as Acute retinal pigment epitheliitis (ARPE), is a rare, idiopathic, self-limiting inflammatory disorder of the macula first described in 1972 by Krill and Deutman in six patients aged 16–46 years. It predominantly affects healthy young adults (20–50 years) without sex or racial predilection, presenting with sudden onset of central vision disturbance that typically resolves within 6–12 weeks with near-complete visual recovery in most cases EyeWikiPMC. Histopathologically, lesions consist of small, round, dark gray spots in the macula, each surrounded by a yellow-white halo; spectral-domain OCT localizes the primary site of inflammation to the photoreceptor-RPE interface (interdigitation zone), rather than the RPE alone EyeWikiEyeWiki. No specific treatment is required, as spontaneous resolution occurs in the vast majority of patients EyeWikiPMC.

Types

Unilateral ARPE
In roughly 75–90 % of cases, ARPE affects only one eye. Patients report abrupt, painless visual disturbance in a single eye, with funduscopy revealing the characteristic macular spots. Optical coherence tomography (OCT) shows a dome-shaped hyperreflective lesion at the outer retinal layers disrupting the ellipsoid and interdigitation zones BioMed CentralEyeWiki.

Bilateral ARPE
Although uncommon (≈10 %), bilateral involvement can occur either simultaneously or sequentially. Bilateral ARPE often follows the same natural history as unilateral disease, with symmetric or asymmetric presentation of scotomas and fundus lesions PMCEyeWiki.

Recurrent ARPE
Recurrences are exceedingly rare (< 5 %), but have been documented in a handful of case reports. Recurrent episodes tend to mirror the initial presentation, with new macular lesions and visual symptoms followed by spontaneous resolution PubMed.

Atypical ARPE
Atypical variants may present with more extensive fundus involvement, deviations from the classic halo-ring appearance, or prolonged recovery beyond 12 weeks. These cases require careful multimodal imaging to distinguish from other white-dot syndromes ResearchGate.

Etiology and Causes

The precise etiology of ARPE remains unknown; it is classified as idiopathic. However, several documented associations and hypothesized triggers have emerged:

1. Idiopathic (Unknown Cause)
   By definition, most cases of ARPE cannot be linked to any specific underlying factor EyeWiki.

2. Viral Infection (Influenza-Like Prodrome)
   Approximately 17 % of patients report flu-like symptoms 1–2 weeks before ARPE onset, suggesting a viral trigger in at least some cases EyeWikiEyeWiki.

3. Picornavirus Infection
   Case series have documented ARPE following picornavirus exposure, implicating enterovirus-type agents in pathogenesis Eco-Vector Journals Portal.

4. Hepatitis C Virus
   Isolated reports link ARPE onset to acute hepatitis C infection, suggesting hepatotropic viruses may provoke retinal inflammation Eco-Vector Journals Portal.

5. Coxsackie A Virus
   A case report described ARPE developing after Coxsackie A infection, further supporting the role of non-enveloped RNA viruses SciELO.

6. Post-Vaccination Immune Response
   Small case series note ARPE onset following immunizations (e.g., seasonal influenza, COVID-19 vaccines), raising the possibility of vaccine-triggered immune activation Karger.

7. Ischemia of the Deep Capillary Plexus
   Analogous to acute macular neuroretinopathy, ischemic injury to the deep retinal capillaries has been postulated as a contributing mechanism EyeWiki.

8. Autoimmune-Mediated Inflammation
   Similar to other white-dot syndromes, an aberrant immune response—potentially involving immune complex deposition—may underlie the inflammation touchOPHTHALMOLOGY.

9. Genetic Predisposition
   While no specific genes have been identified for ARPE, related white-dot conditions (e.g., APMPPE) show familial clustering, suggesting genetic susceptibility Wikipedia.

10. Parainfectious Immune Reaction
    Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) often follows systemic infections, indicating a parainfectious immune mechanism that may also apply to ARPE Wikipedia.

11. Other Viral Agents
    Though specific associations are limited, other viruses (adenovirus, Epstein–Barr virus) have been hypothesized based on the broader spectrum of post-viral white-dot syndromes.

12. Systemic Autoimmune Disorders
    Conditions such as sarcoidosis and Behçet’s disease can affect the outer retina; their shared immunopathology raises the possibility of overlap in ARPE PMC.

13. Environmental Triggers
    Exposures (e.g., ultraviolet light, toxins) are speculative but warrant investigation given environmental links in other retinal inflammations.

14. Medication-Induced Hypersensitivity
    Hypersensitivity reactions to systemic drugs could theoretically provoke a localized RPE response; however, no definitive cases have been reported.

15. Stress-Related Immune Modulation
    Psychological or physiological stress can alter immune homeostasis, potentially tipping the balance toward retinal inflammation.

Note: Except for the first ten items—supported by clinical reports and imaging studies—the remaining causes are theoretical hypotheses requiring further research.

Symptoms

Although ARPE’s hallmark is macular inflammation seen on imaging, patients commonly experience:

1. Acute Painless Loss of Vision
   Sudden, painless reduction in central vision is the most frequent complaint EyeWiki.

2. Central Scotoma
   A blind spot in the central visual field, detectable on self-testing (e.g., Amsler grid) and formal perimetry EyeWiki.

3. Blurred Vision
   Generalized blurring, distinct from scotoma, reported by many patients SciELO.

4. Metamorphopsia
   Visual distortion (straight lines appearing wavy) on Amsler grid testing SciELO.

5. Photopsia
   Flashes of light or shimmering phenomena, occasionally reported by analogy to other white-dot syndromes NCBI.

6. Floaters
   Perception of small moving spots, inferred from similarities with inflammatory retinal disorders NCBI.

7. Photophobia
   Light sensitivity, seen in many uveitic and white-dot conditions NCBI.

8. Dyschromatopsia
   Mild color perception changes, analogous to findings in related maculopathies Wikipedia.

9. Reduced Contrast Sensitivity
   Difficulty discerning low-contrast objects, consistent with photoreceptor-RPE disruption NCBI.

10. Night Vision Difficulties
    Impaired scotopic vision, sometimes seen in outer-retinal inflammatory disorders NCBI.

Diagnostic Tests

A multimodal approach is key, combining clinical examination with manual tests, laboratory workup, electrodiagnostic studies, and imaging.

Physical Examination

• Best-Corrected Visual Acuity (BCVA)
  Quantifies central vision loss; typical presentation is 20/40 (range 20/30–20/100) EyeWiki.

• Slit-Lamp Biomicroscopy
  Rules out anterior segment inflammation; findings in ARPE are normally unremarkable EyeWiki.

• Intraocular Pressure Measurement
  Ensures no secondary pressure elevation; pressures are typically normal in ARPE.

• Dilated Fundus Examination
  Reveals fine macular pigment stippling with surrounding hypopigmented halos EyeWiki.

Manual Tests

• Amsler Grid Test
  Detects central scotoma and metamorphopsia through patient-reported grid distortions EyeWiki.

• Ishihara Color Vision Test
  Screens for dyschromatopsia; may show mild color deficits in ARPE Wikipedia.

• Confrontation Visual Field Test
  Provides a quick bedside check for field defects, confirming central scotoma.

Laboratory and Pathological Tests

• Complete Blood Count (CBC)
  Evaluates for systemic infection or inflammation.

• Erythrocyte Sedimentation Rate (ESR) & C-Reactive Protein (CRP)
  Assess systemic inflammatory activity.

• Hepatitis C Serology
  Screens for HCV, given reported associations Eco-Vector Journals Portal.

• Viral Panel / PCR for Picornavirus
  Detects picornaviral RNA in serum, supporting viral etiologies Eco-Vector Journals Portal.

Electrodiagnostic Tests

• Multifocal Electroretinogram (mfERG)
  Reveals focal depression of retinal responses in the macula EyeWiki.

• Electro-Oculogram (EOG)
  May show reduced Arden ratio, reflecting RPE dysfunction EyeWiki.

• Full-Field Electroretinography (ffERG)
  Assesses global retinal function; usually normal in ARPE Wikipedia.

• Visual Evoked Potential (VEP)
  Evaluates post-retinal visual pathway integrity; generally unaffected in isolated ARPE Wikipedia.

Imaging Tests

• Optical Coherence Tomography (OCT)
  The investigation of choice; shows dome-shaped hyperreflective lesions disrupting the ellipsoid and interdigitation zones EyeWikiEyeWiki.

• Fluorescein Angiography (FA)
  Demonstrates a transmission window defect (hyperfluorescence) without leakage in ≈83 % of cases EyeWikiEyeWiki.

• Indocyanine Green Angiography (ICGA)
  May show late-phase hyperfluorescence in some eyes; often unremarkable EyeWikiEyeWiki.

• Fundus Autofluorescence (FAF)
  Can reveal increased autofluorescence at lesion sites EyeWikiEyeWiki.

• Optical Coherence Tomography Angiography (OCT-A)
  Assesses capillary perfusion and can exclude neovascular complications; used in advanced multimodal imaging BioMed Central.

Non-Pharmacological Treatments

Below are 20 supportive and rehabilitative approaches—spanning physiotherapy/electrotherapy, exercise, mind-body techniques, and self-management education—that may help maintain retinal health, support visual recovery, or alleviate symptoms in ARPE.

A. Physiotherapy & Electrotherapy Therapies

1. Transpalpebral Electrical Stimulation
   Description & Mechanism: Delivers low-current pulses across closed eyelids to stimulate RPE cells and retinal neurons. Animal and early human studies suggest it may promote neurotrophic factor release and reduce inflammation.
   Purpose: Potentially accelerates recovery of photoreceptor integrity. Frontiers

2. Non-Invasive Electrical Stimulation (ES)
   Description & Mechanism: Electrodes placed on the forehead and temples deliver microampere currents, enhancing retinal blood flow and exerting neuroprotective, anti-inflammatory effects.
   Purpose: May preserve or restore visual function in inflammatory retinal conditions. BioMed Central

3. Photobiomodulation (PBM)
   Description & Mechanism: Low-level visible to near-infrared light (600–1,000 nm) applied externally to the eye, modulating mitochondrial function, reducing oxidative stress, and curbing inflammation.
   Purpose: Supports RPE and photoreceptor health; under investigation in retinal degenerations. PentaVision

4. Low-Level Light Therapy (LLLT)
   Description & Mechanism: Similar to PBM, uses specific wavelengths (e.g., 670 nm) to stimulate cytochrome c oxidase in mitochondria.
   Purpose: Aims to speed lesion resolution and photoreceptor recovery. PentaVision

5. Biofeedback Visual Rehabilitation
   Description & Mechanism: Uses real-time feedback (microperimetry) to train fixation stability and enhance remapping of central visual field.
   Purpose: Improves use of unaffected retinal areas for clearer vision. TVST

6. Transcranial Direct Current Stimulation (tDCS)
   Description & Mechanism: Delivers weak electrical currents through scalp electrodes to modulate visual cortex excitability.
   Purpose: May enhance visual processing post-retinal injury.

7. Magnetotherapy
   Description & Mechanism: Applies pulsed electromagnetic fields near the eye, theorized to boost microcirculation and reduce inflammation.
   Purpose: Supports retinal recovery, though clinical evidence is limited.

8. Ocular Microcurrent Therapy
   Description & Mechanism: Microampere currents delivered directly to periocular tissues to stimulate cellular repair pathways.
   Purpose: Aims to support RPE renewal and photoreceptor function.

9. Optical Coherence Tomography (OCT) Biofeedback
   Description & Mechanism: Real-time OCT imaging guides patients in subtle eye movements to optimize fixation on healthier retinal patches.
   Purpose: Enhances visual performance during recovery.

10. Vision Restoration Therapy (Computer-Based)
    Description & Mechanism: Interactive software prompts saccadic training and peripheral awareness exercises.
    Purpose: Strengthens alternative visual pathways when central vision is affected.

B. Exercise Therapies

11. Saccadic Eye-Movement Drills
    Practice rapid, targeted eye movements to improve switching between fixation points.

12. Accommodation Flexibility Training
    Alternating focus between near and distant targets to maintain lens flexibility and reduce eye strain.

13. Contrast Sensitivity Exercises
    Viewing high-contrast patterns at varying distances to sharpen visual discrimination.

14. Fixation Stability Workouts
    Focusing on small targets to enhance steadiness and reduce micro-tremor.

15. Dynamic Range Scanning
    Tracking moving dots or objects across the visual field to maintain peripheral awareness.

C. Mind-Body Therapies

16. Mindfulness Meditation
    Guided relaxation focusing on breath, which may lower systemic stress and indirectly support retinal healing.

17. Progressive Muscle Relaxation
    Sequentially tensing and relaxing facial and ocular muscles to reduce periorbital tension.

18. Guided Imagery
    Visualization exercises that promote ocular blood flow and calm neural pathways.

D. Educational Self-Management

19. Patient Education Sessions
    Learning about ARPE’s natural course, symptom tracking, and the importance of follow-up examinations.

20. Symptom Diary & Self-Monitoring
    Recording vision changes (e.g., scotoma size, photopsias) to inform timely clinical reviews.

 Drugs (Evidence-Based)

Though ARPE is self-resolving and typically requires no medication, case reports have explored anti-inflammatory agents to hasten recovery. Below are the most documented options:

1. Oral Prednisone (Systemic Corticosteroid)

   • Dosage: ~1 mg/kg/day for 1–2 weeks, then taper

   • Class: Glucocorticoid

   • Timing: Once daily in morning

   • Side Effects: Weight gain, hyperglycemia, mood swings, osteoporosis EyeWiki

2. Intravenous Methylprednisolone (Pulsed Steroid)

   • Dosage: 1 g/day for 3 days

   • Class: Corticosteroid

   • Timing: Single daily infusion

   • Side Effects: Fluid retention, hypertension, immunosuppression Lippincott Journals

3. Prednisolone Acetate 1% Eye Drops (Topical Steroid)

   • Dosage: 1 drop QID for 5–7 days

   • Class: Corticosteroid

   • Timing: Morning, midday, afternoon, evening

   • Side Effects: Elevated intraocular pressure, cataract risk BioMed Central

4. Oral Ibuprofen (NSAID)

   • Dosage: 400 mg every 6 hours as needed

   • Class: Non-steroidal anti-inflammatory

   • Timing: With meals to reduce GI upset

   • Side Effects: Gastric irritation, renal impairment PubMed

5. Ketorolac Tromethamine 0.5% Eye Drops (Topical NSAID)

   • Dosage: 1 drop QID for 1 week

   • Class: NSAID

   • Side Effects: Corneal toxicity with prolonged use

6. Naproxen (Oral NSAID)

   • Dosage: 250 mg BID

   • Class: NSAID

   • Side Effects: GI upset, headache

7. Acetazolamide (Carbonic Anhydrase Inhibitor)

   • Dosage: 250 mg TID

   • Class: Diuretic

   • Purpose: May reduce subretinal fluid

   • Side Effects: Paresthesias, electrolyte imbalance

8. Pentoxifylline (Microcirculation Enhancer)

   • Dosage: 400 mg TID

   • Class: Phosphodiesterase inhibitor

   • Side Effects: Dizziness, GI upset

9. Doxycycline (Tetracycline Antibiotic)

   • Dosage: 100 mg BID for 5–7 days

   • Class: Antibiotic/anti-inflammatory

   • Side Effects: Photosensitivity, GI upset

10. Low-Dose Aspirin (Antiplatelet)

    • Dosage: 81 mg daily

    • Class: Salicylate

    • Side Effects: Bleeding risk

Dietary Molecular Supplements

Although ARPE is not driven by nutritional deficiency, antioxidants and micronutrients that support retinal health are commonly recommended:

1. Vitamin C – 500 mg/day (Antioxidant) en.wikipedia.org

2. Vitamin E – 400 IU/day (Lipid antioxidant) en.wikipedia.org

3. Zinc – 80 mg/day (Cofactor for antioxidant enzymes) en.wikipedia.org

4. Copper – 2 mg/day (Balance zinc levels) en.wikipedia.org

5. Beta-Carotene – 15 mg/day (Precursor to vitamin A) en.wikipedia.org

6. Lutein – 10 mg/day (Macular pigment) en.wikipedia.org

7. Zeaxanthin – 2 mg/day (Macular pigment) en.wikipedia.org

8. Omega-3 Fatty Acids – 1,000 mg DHA/EPA daily (Anti-inflammatory)

9. Anthocyanins – 80 mg bilberry extract/day (Capillary strength)

10. Resveratrol – 100 mg/day (Anti-oxidative)

Advanced “Bisphosphonate, Regenerative, Viscosupplementation, Stem Cell” Drugs

While none are approved specifically for ARPE, the following emerging retinal therapies illustrate cutting-edge approaches with potential future applicability:

1. ABBV-RGX-314 (AAV8-Delivered Anti-VEGF Gene Therapy)

   • Administration: 1–2 suprachoroidal injections in wet AMD trials

   • Mechanism: AAV8 vector drives intraocular anti-VEGF antibody expression to reduce neovascular risk.

   • Status: Phase II AAVIATE trial showed stable BCVA with 80% fewer injections over 6 months Ophthalmology Advisor

2. Encapsulated Cell-Based CNTF Implant (NT-501 / Encelto)

   • Dosage: Low-dose releases ~5 ng/day; high-dose ~20 ng/day of CNTF into vitreous

   • Mechanism: Sustained ciliary neurotrophic factor delivery to support photoreceptor survival.

   • Status: Phase I/II trials demonstrated safety and potential for photoreceptor stabilization PubMedPMC

3. Intravitreal Hyaluronic Acid (Healon-H)

   • Dosage: Single injection (typical: 1–2 mL of 1.4% solution)

   • Mechanism: Viscosupplementation to aid retinal reattachment and protect retinal layers during surgery.

   • Evidence: Used in complicated retinal detachment with long-term safety PubMed

4. Hyaluronic Acid Nanoparticles (HA-NS)

   • Dosage: Experimental intravitreal micro-doses of HA-coated nanoparticles

   • Mechanism: Targeted drug/gene delivery to RPE via CD44 receptor binding, enhancing penetration and controlled release.

   • Evidence: Improved outer retinal targeting in preclinical models PMC

5. Autologous CD34+ Stem Cell Intravitreal Injection

   • Dosage: Single injection of purified CD34+ bone marrow-derived cells (~10^5–10^6 cells)

   • Mechanism: Homing of progenitor cells to damaged retina, release of neurotrophic factors, promoting repair.

   • Evidence: Phase 1 RP trial showed safety and some visual improvements in 4/7 participants UC Davis Health

6. ESC-Derived RPE Cell Sheet (ASP7317)

   • Dosage: Subretinal sheet of ~200,000 RPE cells (Phase Ib)

   • Mechanism: Replaces damaged RPE, supporting photoreceptor function and preventing atrophy.

   • Status: Under investigation for geographic atrophy in dry AMD en.wikipedia.org

Surgeries (Procedures & Benefits)

Although ARPE seldom requires surgery, the following retinal procedures underpin management of more severe or misdiagnosed conditions:

1. Pars Plana Vitrectomy

   • Procedure: Removal of vitreous gel via three small incisions at the pars plana.

   • Benefits: Clears vitreous opacities, relieves traction on retina, and allows access for subretinal therapies.

2. Subretinal Cell or Gene Delivery

   • Procedure: Micro-incision and cannula placement under retina to inject therapeutic cells or vectors.

   • Benefits: Direct delivery to RPE/photoreceptors for regenerative or gene therapy.

3. Epiretinal Membrane Peeling

   • Procedure: Microsurgical removal of fibrous membranes on retinal surface.

   • Benefits: Restores retinal architecture, improves vision if epiretinal traction coexists.

4. Laser Photocoagulation

   • Procedure: Focal or grid application of laser burns to RPE.

   • Benefits: Stabilizes microaneurysms or focal leaks; not typically used in ARPE but in differential diagnoses.

5. Scleral Buckling

   • Procedure: External silicone band placed around eye equator to support retina.

   • Benefits: Treats rhegmatogenous retinal detachment; underscores importance of accurate diagnosis before ARPE misdiagnosis.

Preventions

1. Avoid Unnecessary Steroid Use (systemic or topical)

2. Protect Against Viral Illnesses (hand hygiene, vaccinations)

3. Manage Stress & Sleep to support immune balance

4. Use UV-Blocking Sunglasses outdoors

5. Maintain Balanced Diet rich in antioxidants

6. Control Blood Sugar & Blood Pressure

7. Schedule Regular Eye Exams after any sudden vision changes

8. Avoid Smoking (oxidative risk)

9. Limit Screen Time and take frequent breaks (20-20-20 rule)

10. Stay Hydrated to maintain ocular perfusion

When to See a Doctor

• Persistent or enlarging central scotoma

• Sudden drop in central visual acuity

• New onset of metamorphopsia (distorted vision)

• Photophobia or light intolerance

• Any unexplained visual field defect

What to Do & What to Avoid

Do:

1. Keep symptom diary and rate vision daily

2. Attend scheduled OCT and visual acuity follow-ups

3. Rest eyes and avoid eye strain

4. Wear sunglasses in bright light

5. Follow your ophthalmologist’s instructions

Avoid:
6. Rubbing or pressing on your eyes
7. Sudden head-jerking movements
8. High-dose systemic steroids without indication
9. Excessive caffeine or alcohol (may affect microcirculation)
10. Self-prescribing eye drops or supplements

Frequently Asked Questions

1. What causes ARPE?
   ARPE’s exact cause is unknown, but many patients report a recent mild viral infection. It’s thought to involve transient RPE inflammation.

2. Is treatment always needed?
   No—ARPE is self-limiting in nearly all cases and resolves without therapy. Treatment is reserved for severe or atypical presentations.

3. How long does recovery take?
   Most recover full vision within 4–8 weeks, although OCT changes may persist longer.

4. Can ARPE recur?
   Recurrences are exceedingly rare (<5% in small series).

5. Will I have permanent vision loss?
   In >90% of cases, vision returns to 20/20 with no lasting scotoma.

6. Should I get antiviral medications?
   No evidence supports antivirals; focus remains on observation and supportive care.

7. Are imaging tests necessary?
   Yes—OCT and fluorescein angiography confirm diagnosis and exclude other maculopathies.

8. Can I drive during recovery?
   If your vision drops below legal limits, avoid driving until it recovers.

9. Is genetic testing helpful?
   Genetic testing is not indicated for ARPE, as it is not inherited.

10. Should I stop wearing contact lenses?
    You may continue if comfortable, but switch to glasses if lenses irritate your eyes.

11. Can pregnancy trigger ARPE?
    No known link, though pregnancy-related immune changes affect other ocular diseases.

12. Does ARPE affect both eyes?
    It’s usually unilateral but can be bilateral in ~20% of cases.

13. Should I take AREDS supplements?
    They support overall retinal health but have not been studied in ARPE specifically.

14. Can stress worsen symptoms?
    High stress may exacerbate perception of vision changes; mind-body techniques can help.

15. When is surgery considered?
    Surgery is not used for ARPE itself but for complications misdiagnosed as other retinal detachments.

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: July 10, 2025.

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