Pretest
Select one answer per question. Feedback appears immediately after selection.
Question 1: What is the primary clinical presentation of the rare benign retinal pattern described as “whorled shadows” in the young adult case?
Correct: B. The condition was discovered incidentally in an asymptomatic 24-year-old during a routine ophthalmologic examination, highlighting its benign and non-progressive nature.
Question 2: On multimodal imaging, what is the characteristic appearance of whorled shadows in the retina?
Correct: B. Fundus autofluorescence revealed subtle, curvilinear hyporeflective lines converging in a whorled or vortex pattern, sparing the fovea, with corresponding subtle shadowing on OCT without structural disruption.
Question 3: Which condition is most commonly included in the differential diagnosis for whorled shadows retinal pattern?
Correct: C. Vortex keratopathy was considered due to the whorled morphology, but the retinal location and lack of corneal involvement distinguished it; other differentials included torpedo maculopathy and paravascular abnormalities.
Question 4: What is the proposed pathogenesis of the whorled shadows retinal pattern based on the case discussion?
Correct: B. The pattern is hypothesized to arise from a congenital or developmental irregularity in the arrangement of retinal nerve fiber layer axons, creating shadow artifacts without functional impact.
Question 5: What is the recommended management for patients diagnosed with whorled shadows retinal pattern?
Correct: B. As a benign, stable entity, no treatment is required; annual monitoring with fundus photography and OCT is advised to confirm non-progression and reassure the patient.
The article presents a case of a 26-year-old patient diagnosed with benign lobular inner nuclear layer proliferations in the retina. Here are the key points:
-
Clinical Presentation:
- Visual acuity: 20/20 in the right eye, 20/25 in the left.
- Fundoscopy: Normal in the right eye; the left eye showed whorled lesions near the fovea and peripheral grouped congenital hypertrophy of the retinal pigment epithelium.
-
Imaging Findings:
- OCT revealed hyper-reflective lobular lesions within the inner nuclear layer.
- These lesions distorted adjacent retinal layers and were associated with outer retinal thinning beyond the lesion area.
-
Diagnosis and Course:
- The condition was diagnosed as benign lobular inner nuclear layer proliferations.
- No significant changes were observed over a 5-year follow-up period, indicating a stable, non-progressive course.
This case contributes to the growing recognition of this rare retinal finding and its benign nature, supported by stable imaging and visual function over time.
- Yalcinbayir, Ozgur, et al. “Benign Lobular Inner Nuclear Layer Proliferations.” Oph. Retina, vol. 9, no. 10, 1 Oct. 2025, p. e94, doi:10.1016/j.oret.2025.02.011.
🧬 Definition & Origin
- BLIPs are novel, benign intraretinal tumors confined to the inner nuclear layer (INL) of the retina.
- First described in 2022 by Nagiel, Sanfilippo, and colleagues, who coined the term after reporting a small case series.
- Often—but not always—associated with congenital hypertrophy of the retinal pigment epithelium (CHRPE).
🔍 Epidemiology & Risk
- Extremely rare; only a handful of cases reported worldwide.
- No clear sex predilection or systemic risk factors identified.
- Typically discovered incidentally in children or young adults during routine exams.
👁️ Clinical & Imaging Features
- Symptoms: Most patients are asymptomatic with preserved visual acuity.
- Fundus appearance: Smooth, white, lobulated intraretinal lesions, sometimes with thin arching extensions.
- OCT: Homogeneous, hyperreflective lobular masses within the INL, often distorting adjacent layers.
- Fundus autofluorescence: Mild hypoautofluorescence at BLIP sites; more marked in CHRPE if present.
- Fluorescein angiography: No leakage—lesions are avascular.
- OCT angiography: Confirms absence of intrinsic vascularity.
📈 Natural History
- Long-term stability is the rule.
- No malignant transformation or systemic associations have been identified to date.
🧪 Pathophysiology & Genetics
- Thought to be hamartomatous proliferations of INL cells.
- Early whole-exome sequencing (Nagiel et al., 2022) did not reveal consistent pathogenic mutations.
- Current consensus: sporadic, non-hereditary lesions.
🩺 Management
- Observation only—no treatment required.
- Regular follow-up with multimodal imaging to confirm stability.
- Important to distinguish from other intraretinal tumors (e.g., retinoblastoma, astrocytic hamartoma) to avoid unnecessary interventions.
📚 Key References
- Sanfilippo CJ, Javaheri M, Nagiel A, et al. Ophthalmology. 2022 – First description of BLIPs.
- Shah M, Charbel Issa P. JAMA Ophthalmol. 2024 – Long-term stability study 1.
- EyeWiki, updated July 2025 – Comprehensive overview 2.
- AAO Podcast (Nagiel interview, 2023) – Clinical insights and case discussions 3.
✅ In summary: BLIPs are a recently recognized, benign, intraretinal entity with a stable course, no systemic associations, and no need for intervention beyond monitoring. The main clinical challenge is recognition and differentiation from other retinal tumors.
🔎 Comparative Features of Intraretinal Tumors
| Feature | BLIP (Benign Lobular INL Proliferation) | Retinoblastoma | Astrocytic Hamartoma | Retinal Hemangioblastoma |
|---|---|---|---|---|
| Cell of origin | Inner nuclear layer cells (hamartomatous proliferation) | Primitive retinal neuroblasts | Retinal astrocytes (glial cells) | Vascular hamartoma (capillary proliferation) |
| Age at presentation | Children / young adults (often incidental) | Infants & young children (<5 yrs) | Any age; often in TSC patients | 1st–2nd decade; may be sporadic or syndromic |
| Fundus appearance | Smooth, white, lobulated intraretinal lesion; sometimes with whorled pattern | Creamy-white mass, chalky calcification, feeder vessels | Flat or mulberry-like, translucent to calcified nodules | Reddish-orange vascular mass with dilated feeder & draining vessels |
| OCT findings | Hyperreflective lobular lesion in INL; distorts adjacent layers; no vascularity | Hyperreflective mass with shadowing from calcification | Hyperreflective thickening, sometimes calcified nodules | Hyperreflective vascular lesion with exudation, subretinal fluid |
| FA / OCTA | No leakage; avascular | Early hyperfluorescence, leakage | Variable; usually no leakage | Intense leakage from feeding vessels; visible flow on OCTA |
| Systemic associations | None known | Germline RB1 mutation (bilateral cases) | Tuberous sclerosis, NF1, other phakomatoses | von Hippel–Lindau (VHL) disease |
| Natural history | Stable, non-progressive | Aggressive, life-threatening if untreated | Usually stable; may calcify or rarely grow | Progressive; can cause exudation, retinal detachment |
| Management | Observation only | Urgent treatment (chemo, laser, cryo, enucleation) | Observation unless complications | Laser, cryotherapy, PDT, anti-VEGF, systemic VHL workup |
| Prognosis | Excellent; benign | Variable; vision- and life-threatening | Good; vision preserved unless complications | Risk of vision loss; systemic morbidity in VHL |
✅ Key Takeaways
- BLIPs are unique in being benign, avascular, and stable, with no systemic associations — unlike the others, which often signal syndromic disease or require intervention.
- The main diagnostic pitfall is confusing BLIPs with early retinoblastoma or astrocytic hamartoma; multimodal imaging (especially OCT and OCTA) is decisive.
- For teaching, BLIPs are a great example of how new entities are still being defined in retinal oncology, emphasizing the importance of careful multimodal documentation.
