Overview
Definition:
Retinopathy of prematurity (ROP) is a potentially blinding disorder affecting premature infants
It is characterized by abnormal blood vessel development in the retina, primarily in the peripheral retina
This neovascularization can lead to retinal detachment, scarring, and irreversible vision loss if not detected and treated promptly.
Epidemiology:
ROP affects approximately 15-30% of infants born before 30 weeks gestation
The incidence is higher in very low birth weight (VLBW) infants (<1500g)
Factors associated with increased risk include low gestational age, low birth weight, prolonged oxygen therapy, sepsis, intraventricular hemorrhage, and apnea
In India, ROP is a significant cause of childhood blindness, with an estimated 20-30% of premature babies developing the condition.
Clinical Significance:
ROP is a leading cause of preventable blindness in premature infants globally
Early and regular screening is crucial for timely intervention, preventing severe visual impairment and blindness
Understanding current screening guidelines and the evolving role of anti-VEGF therapy is paramount for pediatricians and ophthalmologists managing these vulnerable infants, directly impacting long-term visual outcomes and quality of life
This knowledge is frequently tested in DNB and NEET SS examinations.
Screening Schedule
Risk Factors:
Infants born at < 30 weeks gestation or with birth weight < 1500g require screening
Other risk factors include fluctuating oxygen levels, sepsis, anemia, and a history of intraventricular hemorrhage
A Gestational Age (GA) of 31-33 weeks is also often considered high risk for requiring screening.
Initial Examination:
The first eye examination should be performed by an experienced ophthalmologist using indirect ophthalmoscopy or wide-field retinal imaging (e.g., Optos) via dilated pupils
The examination should occur between 4-6 weeks of chronological age or by 30-32 weeks post-menstrual age (PMA), whichever is later.
Follow Up Intervals:
The frequency of follow-up examinations is determined by the presence and stage of ROP
If no ROP is present at the initial examination, examinations are typically repeated every 1-2 weeks
If ROP is detected, closer follow-up (e.g., every 4-7 days) is indicated based on the International Classification of ROP (ICROP3) staging.
Discontinuation Criteria:
Screening can be discontinued when the infant reaches 45-47 weeks PMA, the retina is fully vascularized, and there is no evidence of active ROP or residual structural damage
Premature infants who have required treatment may need lifelong ophthalmological follow-up due to the risk of late complications.
Special Considerations:
Infants with significant medical issues requiring prolonged hospitalization or fluctuating oxygen therapy may need earlier or more frequent screening
Consensus guidelines and institutional protocols should be followed meticulously.
Classification And Staging
International Classification:
The International Classification of Retinopathy of Prematurity (ICROP) is used to stage ROP
It divides the retina into three zones and the disease into five stages, along with "plus disease" (venous dilation and arterial tortuosity) and "regressed ROP." Zone I is the most posterior and severe, Zone III is the most peripheral
Stage 1: Demarcation line
Stage 2: Ridge
Stage 3: Ridge with extra-retinal neovascularization
Stage 4: Partial retinal detachment
Stage 5: Total retinal detachment.
Zone And Clock Hour:
Zone I is a circle with radius from the optic disc to the macula
Zone II is a circle from the junction of Zone I and II to the nasal ora serrata
Zone III is the temporal crescent
ROP is also described by its extent in clock hours, indicating the circumferential involvement of the retina.
Plus Disease:
Plus disease is a critical indicator of disease severity and the need for treatment
It is characterized by increased tortuosity and dilation of the retinal blood vessels anterior to the demarcation line or abnormal neovascularization
Its presence signifies aggressive ROP.
Threshold Rop:
Threshold ROP is defined as Stage 3 ROP in Zone I or II, with at least 5 continuous or 8 cumulative clock hours of involvement, and with Plus disease
This is the stage at which treatment is strongly recommended to prevent poor visual outcomes.
Late Stage Rop:
Stages 4 and 5 ROP represent partial and total retinal detachments, respectively
These are critical surgical emergencies with poor visual prognosis, even with timely intervention.
Anti Vegf Considerations
Role Of Vegf:
Vascular Endothelial Growth Factor (VEGF) plays a critical role in the pathogenesis of ROP
In the ischemic retina of premature infants, elevated VEGF stimulates abnormal neovascularization, leading to the characteristic findings of ROP
Anti-VEGF agents inhibit this process.
Indications For Anti Vegf:
Anti-VEGF agents (e.g., bevacizumab, ranibizumab) are typically used for aggressive posterior ROP (APROP), especially in Zone I or posterior Zone II, or when laser photocoagulation or cryotherapy is not feasible or likely to be effective
They are also used off-label in some cases of threshold ROP with plus disease, often in conjunction with laser treatment.
Drug Choices And Dosing:
Bevacizumab (Avastin) and ranibizumab (Lucentis) are the most commonly used anti-VEGF agents
Dosing is typically intravitreal, with bevacizumab commonly used at 0.05 mg/0.1 ml per eye, and ranibizumab at 0.2 mg/0.1 ml per eye
Doses and administration should strictly follow ophthalmic surgical protocols and institutional guidelines.
Advantages And Disadvantages:
Advantages of anti-VEGF therapy include reduced retinal damage, preservation of peripheral vision, and potentially less discomfort compared to laser or cryotherapy
Disadvantages include the risk of systemic absorption and potential long-term effects on ocular growth and development, although current evidence suggests generally good safety profiles
Systemic absorption can lead to transient suppression of VEGF levels, which might theoretically affect other developing organs, particularly the lungs and bone marrow, although significant clinical sequelae are rare.
Comparison With Laser Therapy:
Laser photocoagulation (ablating avascular retina) has been the gold standard
Anti-VEGF therapy is often considered an adjunct or alternative, particularly for posterior ROP
Studies suggest comparable efficacy to laser for threshold ROP, with better peripheral visual field outcomes
Combination therapy of laser and anti-VEGF may offer advantages in certain complex cases
However, laser is a definitive treatment for the avascular retina, while anti-VEGF is a pharmacologic intervention that may require repeat injections and does not eliminate the need for monitoring for recurrence or late complications.
Management Of Rop
Laser Photocoagulation:
Indicated for threshold ROP
Targets the avascular peripheral retina to ablate neovascularization and prevent progression
Typically performed with a diode laser.
Cryotherapy:
An alternative to laser photocoagulation, particularly useful when indirect ophthalmoscopy is difficult or when laser delivery is challenging
It involves freezing the peripheral avascular retina.
Vitreoretinal Surgery:
Indicated for advanced ROP with retinal detachment (Stages 4 and 5)
Surgical options include scleral buckling, vitrectomy, or combined procedures, with the goal of reattaching the retina and preserving some vision
Outcomes are generally poorer in later stages.
Pharmacological Management:
Primarily anti-VEGF injections, as discussed above, for aggressive posterior ROP or selected cases of threshold ROP
Supportive medical management of the premature infant (e.g., oxygenation, sepsis management, nutritional support) is critical for overall outcomes.
Follow Up After Treatment:
Intensive follow-up is required for infants who have undergone treatment for ROP
This includes regular ophthalmological examinations to monitor for recurrence, complications (e.g., strabismus, amblyopia, glaucoma, refractive errors), and to assess visual development.
Complications And Prognosis
Ocular Complications:
Common complications include strabismus, myopia, astigmatism, amblyopia, glaucoma, cataracts, and visual field defects
Retinal detachment is the most severe complication, leading to significant vision loss or blindness
Scarring and dragging of the retina can lead to distorted vision.
Systemic Factors:
The overall health and stability of the premature infant significantly influence ROP management and outcomes
Systemic comorbidities can complicate treatment and recovery.
Prognostic Factors:
Early detection and treatment are the most crucial prognostic factors
The stage of ROP at diagnosis, the zone of involvement, the presence of plus disease, and the promptness and efficacy of intervention all impact the visual prognosis
Infants with higher stages of ROP and significant retinal detachment have a poorer visual outcome.
Long Term Follow Up:
Lifelong ophthalmological follow-up is recommended for infants treated for ROP, especially those with residual retinal abnormalities or a history of significant ROP
This monitoring helps detect and manage late-onset complications such as glaucoma, retinal detachment, and refractive errors.
Key Points
Exam Focus:
Know the high-risk infants for ROP, the specific gestational age/birth weight cutoffs for screening, the timing of the first and subsequent eye exams, and the criteria for discontinuing screening
Understand the ICROP staging and the definition of threshold ROP and plus disease
Be familiar with the indications, agents, and general principles of anti-VEGF therapy in ROP management
Recall the primary treatment modalities: laser, cryotherapy, and surgery, and their respective indications.
Clinical Pearls:
Always consider ROP in any infant born prematurely, especially with low birth weight
Fluctuating oxygenation is a major modifiable risk factor
ensure stable oxygen management
Thorough, dilated fundus examination is essential for diagnosis
Early referral to a pediatric ophthalmologist is critical when ROP is suspected or diagnosed
Anti-VEGF therapy is an evolving modality
be aware of its current role and limitations.
Common Mistakes:
Missing the screening window for premature infants
delaying the first eye examination
Inadequate dilation or incomplete retinal examination
Underestimating the severity of ROP, especially plus disease
Not initiating timely treatment for threshold ROP
Misunderstanding the indications for anti-VEGF therapy or performing it without appropriate indication or follow-up
Inadequate long-term follow-up for treated infants.