What is the recommended examination and treatment approach for a patient suspected of having retinopathy of prematurity (ROP) or significant retinal findings, such as those described in plus disease (HEVR)?

Retinopathy of Prematurity (ROP): Differentials and Examination Findings in Plus Disease

Infants at risk for ROP should undergo systematic dilated fundoscopic examination beginning at 31 weeks postmenstrual age or 4 weeks after birth (whichever is later), with specific attention to vascular tortuosity and dilation in the posterior pole, as plus disease is now the primary indication for laser treatment. 1

Key Differential Diagnoses for ROP

When evaluating an infant with suspected ROP, consider these alternative diagnoses that can present with leukocoria or abnormal retinal findings:

• Persistent Hyperplastic Primary Vitreous (PHPV): Associated with microphthalmia and absence of calcification on imaging, distinguishing it from retinoblastoma 1
• Retinoblastoma: Presents with calcification on CT and contrast enhancement on MRI, typically in normal-sized globes 1
• Coats Disease: Shows absence of calcification and occurs in normal-sized globes, unlike ROP which may show microphthalmia 1
• Congenital Cataract: Can obscure fundoscopic view and requires differentiation through clinical examination 1

Essential Examination Components for ROP/Plus Disease

Initial Clinical Assessment

The examination must systematically evaluate specific features that determine treatment urgency:

• Visual acuity testing (age-appropriate): Baseline VA is the strongest prognostic factor for final visual outcome 2
• Pupillary assessment: Look for relative afferent pupillary defect, which corresponds to ischemia severity and predicts neovascularization risk 2, 1
• Intraocular pressure measurement: Essential to detect early neovascular glaucoma 1, 3
• Slit-lamp biomicroscopy: Examine for iris neovascularization before dilation 1
• Gonioscopy before dilation: Critical when neovascularization is suspected or IOP is elevated 1

Dilated Fundoscopic Examination - Specific ROP Findings

Plus Disease (HEVR - Hemorrhage, Exudates, Venous dilation, Retinal tortuosity):

• Vascular tortuosity: Abnormal tortuosity of arterioles in the posterior pole, which can increase by 217% over 6.2 weeks as plus disease develops 4
• Venous dilation: Abnormal dilation of venules, typically increasing by 28% over 5.1 weeks during progression 4
• Pre-plus disease: An intermediate level of vascular abnormality that carries a 70% risk of requiring laser treatment within 1.6 weeks (mean) 5
• Location (Zone): Document whether disease is in Zone I (most posterior), Zone II (mid-periphery), or Zone III (far periphery) 5
• Stage: Grade from 1-5 based on severity of vascular changes and retinal detachment 5

Critical Examination Pitfalls

Diagnostic variability is substantial: Even experienced ROP examiners disagree on plus disease diagnosis in 10% of cases and on pre-plus disease in 21-32% of cases, particularly when evaluating borderline findings 6. This underscores the need for:

• Serial examinations: Close observation every 1-2 weeks when pre-plus disease is detected 5
• Photographic documentation: RetCam imaging allows for objective comparison over time and consultation 5, 4
• Separate assessment: Evaluate tortuosity and dilation independently, as tortuosity changes are often more dramatic than width changes 4

Peripheral Retinal Examination

Use indirect ophthalmoscopy through dilated pupils to assess: 1

• Extent of vascularization and avascular retina
• Presence of neovascularization elsewhere (NVE) or at the disc (NVD)
• Vitreous or preretinal hemorrhage
• Retinal detachment (Stages 4-5 ROP)

Aggressive Posterior ROP Variant

In developing countries, atypical Aggressive Posterior ROP occurs in heavier birth weight babies and requires heightened vigilance even in infants who might not meet traditional screening criteria 7. This variant can progress rapidly and demands more frequent examination intervals.

Ancillary Testing When Indicated

• Optical Coherence Tomography (OCT): Provides high-resolution macular imaging to detect edema or vitreoretinal interface changes 1
• Fluorescein angiography: Demonstrates extent of ischemia and neovascularization, though rarely needed for ROP diagnosis 1
• Ultrasonography: Essential when media opacity prevents adequate fundoscopic examination 1
• MRI orbits with and without contrast: Reserved for cases where intraocular mass (retinoblastoma) cannot be excluded clinically 1

Treatment Threshold Recognition

Laser photocoagulation is indicated when plus disease is present with: 1

• Zone I or II ROP with sufficient stage progression
• Any level of macular edema threatening vision
• Severe nonproliferative changes with high-risk features

The mean interval from pre-plus disease diagnosis to laser treatment requirement is only 1.6 weeks, making weekly follow-up essential once pre-plus is detected 5.