Retinopathy of Prematurity (ROP)

Types of ROP
Causes and risk factors
Symptoms and signs
Diagnostic tests
Non-Pharmacological Treatments (therapies & others)
Drug Treatments
Dietary “Molecular” Supplements
Regenerative / Stem-cell” Drugs
Procedures / Surgeries
Practical Prevention Steps
When to See Doctors
What to Eat” and “What to Avoid
Frequently Asked Questions

Retinopathy of prematurity, or ROP, is an eye disease that happens in some babies who are born too early and too small. The retina is the light-sensing layer at the back of the eye, and it needs a healthy network of tiny blood vessels to work well. In the womb, these blood vessels grow slowly and steadily from the center of the retina toward the edges during the last months of pregnancy. When a baby is born very early, this normal growth is interrupted. After birth the baby’s oxygen levels, nutrition, infections, and many medical treatments can change the balance of growth signals in the eye. Because of this imbalance, the retinal blood vessels may first stop growing and even shrink, and later they may try to regrow in a fast and disorganized way. These fragile new vessels can leak or bleed and can pull on the retina. If the pulling becomes strong, the retina can lift up and detach, which can lead to permanent vision loss. ROP is therefore a disease that begins with abnormal vessel development and can end with scarring and retinal detachment if it is not recognized and treated in time. Early and regular eye screening is the key, because babies cannot tell us what they see, and the earliest changes are only visible when an eye specialist looks carefully inside the eye.

Retinopathy of Prematurity is an eye condition in very premature or very small newborns. In a full-term baby, the tiny blood vessels of the retina (the “camera film” at the back of the eye) finish growing before birth. In a preterm baby, these vessels are still developing. Because the baby is born early and needs intensive care, oxygen levels, infections, nutrition, and overall stress can disturb normal vessel growth. The vessels may then grow in the wrong way—too fast, too fragile, and in the wrong direction—causing swelling, bleeding, scar tissue, and sometimes pulling the retina off the back of the eye (retinal detachment). If severe and untreated, ROP can lead to permanent vision loss. Early, organized screening and timely treatment dramatically reduce that risk. National Eye Institute

ROP does not affect every premature baby in the same way. Many babies develop only mild changes that heal by themselves. Some babies develop more severe changes that need urgent treatment to prevent damage. The risk depends on how early the baby was born, how small the baby was at birth, how stable the baby’s oxygen levels are after birth, how well the baby grows, and whether the baby has serious illnesses like infections or lung problems. ROP is a preventable cause of childhood blindness when screening and treatment programs are strong and when neonatal care keeps oxygen and nutrition carefully controlled. The sections below explain the types of ROP, the causes and risk factors, the symptoms that families and doctors may notice later, and the tests that doctors use to diagnose and follow the disease.

Types of ROP

Doctors use a simple, step-by-step system to describe where the disease is inside the eye, how severe it is, and how active it is. This common language helps teams decide when to watch closely and when to treat.

Zones (where in the retina the disease is located).
The retina is like a circular map centered on the optic nerve. Doctors divide it into three zones. Zone I is the central area around the optic nerve and macula and is the most important area for sharp vision. Zone II is the middle ring that extends toward the sides. Zone III is the far edge of the retina toward the ear side. Disease in Zone I is more serious because it threatens the area needed for central vision and because it often progresses quickly.

Extent (how much of the circle is involved).
Doctors describe the amount of retina involved using “clock hours.” The retina is imagined like a clock face with 12 sections. More clock hours mean a wider area of disease, and wider areas are more worrisome.

Stages (how far the disease has progressed).

Stage 1 (demarcation line): A thin white line marks the border between the retina that has blood vessels and the retina that does not. This is a very early sign. Many babies with stage 1 get better without treatment.
Stage 2 (ridge): The line becomes a low ridge or wall. This means the vessel growth has stopped and is piling up at the border. Many cases still heal on their own with careful watching.
Stage 3 (extraretinal fibrovascular proliferation): Fragile new vessels and tissue grow on the surface of the retina and into the gel of the eye (the vitreous). These vessels can leak or bleed. This stage has a higher risk of scarring and pulling and often needs treatment when combined with other worrisome signs.
Stage 4 (partial retinal detachment): Scar tissue and contracting vessels pull the retina away from the wall of the eye. Stage 4A spares the center (macula), and Stage 4B involves the center. Treatment is urgent to try to save vision.
Stage 5 (total retinal detachment): The retina is completely detached and forms a funnel shape. This is an emergency and often needs surgery, but the visual prognosis is guarded.

Plus and pre-plus disease (how active the disease is).
Doctors look at the width and twist of the retinal vessels near the optic nerve. When the veins are very wide and the arteries are very twisted, the disease is called plus disease, and that means the eye is very sick and needs treatment. Pre-plus disease means the vessels are more abnormal than normal but not enough to be called full plus disease. Plus disease can appear at different stages and makes the situation more urgent.

Aggressive posterior ROP (AP-ROP).
Sometimes, especially in very tiny infants, the disease begins early, in the back part of the eye (Zone I), and progresses very fast. The vessels are very abnormal, hemorrhages may be present, and the appearance does not always fit the usual stages. This is called aggressive posterior ROP. It requires prompt treatment because it can lead to detachment in days or weeks.

Regressed or cicatricial ROP (healed but with scars).
Even when the active disease goes away, some babies are left with scars, abnormal vessel patterns, dragging of the retina, or changes in the central area. These changes can cause long-term problems like high nearsightedness, lazy eye, eye misalignment, and risk of detachment later in life. These babies need long-term follow-up.

Causes and risk factors

ROP is not caused by a single thing. It is the result of many stresses on a premature baby’s developing retina. Each item below explains a factor in very simple terms and why it matters. The word “cause” here means a risk factor that makes ROP more likely or more severe.

Being born too early (low gestational age).
A baby who is born before the blood vessels in the retina have finished growing faces a higher risk because the growth program is interrupted at a very fragile time.
Very low birth weight.
Smaller babies have less mature organs and less reserve. Their eyes are still building key structures, so any stress can push vessel growth off course.
Rapid changes in oxygen levels after birth.
The retina likes stable oxygen. Big swings from low to high oxygen confuse the growth signals. First the vessels may stop growing, and later they may overgrow in a chaotic way.
Too much oxygen for too long (uncontrolled supplemental oxygen).
Oxygen is life-saving, but if levels are higher than needed for long periods, the normal signals that tell vessels to grow can shut down. When oxygen is reduced later, new vessels may sprout too fast and in the wrong places.
Long time on mechanical ventilation or high oxygen needs.
Babies who need ventilators often have lung disease and unstable oxygen. This ongoing stress increases ROP risk because the retina is exposed to non-physiologic oxygen patterns day after day.
Repeated apnea or bradycardia (breathing pauses and low heart rate).
Each episode can lower oxygen delivery briefly. Many episodes create repeated stress for the retina and can stimulate disorganized vessel growth.
Serious infections (sepsis).
Infection causes inflammation, which releases many chemical signals into the blood. These signals can harm delicate developing vessels and can worsen ROP activity.
Inflammation from gut or lung disease (like necrotizing enterocolitis or bronchopulmonary dysplasia).
Chronic inflammation spreads body-wide. Inflammatory molecules can raise or lower growth factors in harmful ways for the retina.
Poor postnatal weight gain (poor growth).
Good growth reflects steady nutrition and hormones. Poor growth often means low levels of growth factors, and the retina needs those signals to build normal vessels.
Low insulin-like growth factor-1 (IGF-1) in early weeks.
IGF-1 helps vessels grow normally. Very premature babies can have low IGF-1 after birth, and this makes the first phase of retinal vessel growth stall.
Anemia and repeated blood transfusions.
Anemia reduces oxygen delivery, and transfusions may change oxygen handling and iron load. Both can alter retinal oxygen balance and vessel behavior.
Intraventricular hemorrhage or severe brain injury.
These problems reflect overall fragility and instability. Babies with them often have other stresses that also drive ROP risk.
Patent ductus arteriosus (PDA) and its treatment.
A large PDA can steal blood from the body and the retina. The medical or surgical treatments and the swings in blood flow can add more instability.
Fluctuations in carbon dioxide and blood acidity.
CO₂ and pH affect blood vessel tone. Big swings can repeatedly change retinal blood flow, which stresses the developing vasculature.
Hypothermia and unstable body temperature.
Cold stress burns energy, worsens oxygen needs, and can worsen growth failure, all of which raise ROP risk.
Maternal diabetes and placental problems.
When the placenta does not deliver nutrients or oxygen well before birth, the baby can be born smaller and more stressed, which raises ROP risk later.
Multiple gestation (twins or triplets).
Multiples are often born earlier and smaller. They also share placental resources, which can add stress to growth and oxygen balance.
Male sex (slightly higher risk on average).
On average, very small male infants have a somewhat higher risk of complications of prematurity, including ROP, likely due to differences in maturation and hormones.
Genetic susceptibility.
Some babies may be more sensitive to the same level of stress because of their genetic makeup. This does not mean ROP is inherited in a simple way; it means biology is different from baby to baby.
Low intake of key nutrients such as omega-3 fatty acids or inadequate micronutrients.
The retina is rich in omega-3 fats and needs many vitamins and minerals. When nutrition is limited or delayed, vessel growth can be weaker and more disorderly.

Symptoms and signs

Most premature babies with early ROP have no symptoms that parents can see. This is why scheduled eye screening is essential. As children grow, families and doctors may notice signs that suggest current or past ROP or its complications. Each item below is written in plain language to explain what might be seen and what it can mean.

Often no visible symptoms in the early weeks.
ROP in its early stages is silent and can only be found by an eye examination with dilation.
Abnormal or weak red reflex when a light is shined in the eye or in flash photos.
A normal eye shows a bright red or orange glow. If the reflex is patchy, dull, or white, it may mean the retina or lens is not clear.
White pupil (leukocoria).
A white or gray pupil can be a sign of advanced ROP with scarring or detachment, and it needs urgent eye care.
Eyes that do not fix and follow faces or toys at the expected age.
Delayed visual attention can be a sign of poor retinal function or brain-eye connections affected by prematurity.
Nystagmus (shaky or wobbling eye movements).
Fast, small, repeated eye movements can appear when central vision is reduced, and they are a warning sign that vision development is off track.
Strabismus (eyes not pointing in the same direction).
Misalignment can develop after ROP because the eyes have different clarity or focus, or because of scarring that changes eye mechanics.
High nearsightedness (myopia) developing very early.
Children with ROP often become nearsighted because the shape of the eye and the retina’s development were changed.
Unequal focus between the two eyes (anisometropia).
When one eye is much more nearsighted than the other, the brain may favor the clearer eye and ignore the blurrier eye.
Amblyopia (lazy eye) behaviors.
Covering one eye may upset the child more than covering the other if one eye is doing most of the seeing, and this suggests amblyopia.
Sensitivity to light (photophobia).
Some children squint or turn away from light when the retina is irritated or when the eye’s structures are not normal.
Poor night vision or trouble in dim rooms (in older infants or toddlers).
If the peripheral retina is damaged, dark adaptation can be weaker.
Head tilt or unusual head posture to see better.
Children sometimes adopt a posture that lets them use a clearer part of the visual field when the center is weak.
Frequent eye rubbing or squinting.
These behaviors can reflect discomfort, uncorrected refractive error, or effort to sharpen a blurred image.
Delayed visual milestones and poor eye-hand coordination.
If the retina or vision pathways are weak, reaching for small objects and tracking moving items can be delayed.
Gray or cloudy pupil reflection and loss of visual interest in severe cases.
When the retina detaches or the vitreous is cloudy, the pupil can look gray, and the child may stop responding to visual cues. This is an emergency.

Diagnostic tests

ROP is diagnosed by eye examination. Blood tests do not diagnose ROP, but they help understand risk and the baby’s overall condition. Imaging and electrodiagnostic tests help in special cases. Below are 20 tests grouped into physical exam, manual tests, laboratory and pathological tests, electrodiagnostic tests, and imaging tests. Each entry explains what the test is and why it matters.

Physical Exam

Birth risk assessment (gestational age, birth weight, and NICU course review).
Doctors check how early and how small the baby was, and they review oxygen support, ventilation, infections, feeding, and growth. This “paper test” is important because it tells who needs eye screening and how soon.
External eye inspection with a penlight.
The doctor looks at the eyelids, cornea, and front of the eye to make sure the eye can be safely dilated and examined. Any cloudiness or infection in the front of the eye is noted because it can block the view of the retina.
Red reflex screening.
A small light is shined into the eye to see the red glow from the retina. An abnormal or white reflex suggests that the media are not clear or that a serious problem like advanced ROP may be present, and it triggers urgent specialist evaluation.
Pupil light reflex and age-appropriate visual behavior.
The reaction of the pupils and simple observations of visual attention are recorded. These findings do not diagnose ROP, but they help track overall visual function and can reveal other neurologic problems in premature infants.

Manual tests

Dilated binocular indirect ophthalmoscopy (BIO).
This is the core test for ROP. After dilating the pupil with safe drops, the specialist wears a head-mounted light and uses a small lens to view the retina. The doctor maps zones, stages, clock hours, and looks for plus disease. This test is repeated on a schedule until the retina is fully vascularized or the disease has clearly regressed.
Scleral depression during BIO.
A small blunt tool gently presses the white of the eye from the outside to bring the far peripheral retina into view. This lets the doctor see the edges where ROP lives and find subtle stage 3 changes that could be missed without depression.
Direct ophthalmoscopy (limited bedside view when BIO is not available).
A handheld scope gives a narrow view useful for quick checks of the posterior pole. It is not a full ROP exam, but it can identify plus disease or hemorrhage and guide urgent referral.
Cycloplegic retinoscopy (refraction after dilating the focusing muscle).
Once the baby is stable or older, the doctor measures the focusing power of the eyes. Children with ROP often have high myopia or astigmatism, and early glasses can prevent amblyopia.
Cover–uncover and Hirschberg corneal light reflex tests (alignment checks).
As the child grows, simple manual tests detect strabismus. Detecting misalignment early helps start patching or glasses to support brain visual development.
Fixation preference or occlusion test (amblyopia screening).
By gently covering one eye at a time, the examiner sees whether the child uses both eyes equally or strongly favors one. This helps diagnose amblyopia associated with ROP sequelae.

Laboratory and pathological tests

Arterial blood gases and oxygen saturation logs (PaO₂ and SpO₂ review).
These values are not a diagnosis of ROP, but they document exposure to high or fluctuating oxygen, which helps explain risk and guides future oxygen targets.
Complete blood count and hematocrit/hemoglobin.
These tests track anemia and the need for transfusions. Anemia and multiple transfusions are linked to higher ROP risk and help frame the overall picture.
C-reactive protein and blood cultures (infection assessment).
These tests show whether systemic inflammation or sepsis occurred. Infection can make ROP worse and often coincides with periods when the eyes need closer watching.
Nutritional and growth-factor panels when available (e.g., IGF-1 in research settings).
Low IGF-1 and poor protein-energy intake are associated with poor retinal vessel growth. While not routine everywhere, these measurements add insight into risk.

Electrodiagnostic tests

Full-field electroretinography (ffERG).
Small contact lenses or skin electrodes record the retina’s electrical response to flashes of light. ffERG helps evaluate retinal function when the view is poor or when long-term damage is suspected.
Flash visual evoked potentials (VEP).
Electrodes on the scalp record the brain’s response to visual stimuli. VEP helps understand how the visual pathway is working and can be useful when assessing prognosis in children with severe ROP or other neurologic issues.

Imaging tests

Wide-field digital retinal imaging (e.g., RetCam-type systems).
A camera designed for infants takes photos of the entire retina. Images document stages, zones, and plus disease, allow telemedicine screening in some programs, and help families and clinicians follow changes over time.
Wide-field fluorescein angiography (FA).
After placing a small amount of dye into a vein, a special camera photographs the blood flow in the retina. FA shows leakage, areas without vessels, and abnormal shunts, and it is very helpful when planning treatment or evaluating persistent vascular abnormalities.
Handheld optical coherence tomography (OCT).
OCT uses light to make cross-section slices through the retina. In infants it can show subtle swelling near the center, membranes on the retinal surface, early traction, or changes after treatment.
Ocular B-scan ultrasonography.
When blood or scars block the view through the pupil, ultrasound shows the position of the retina and the presence of detachments or membranes. It is essential in advanced disease or before surgery.

Non-Pharmacological Treatments (therapies & others)

Each item includes what it is, purpose, and how it helps.

Careful oxygen targeting & continuous monitoring
Purpose: Protect eyes without risking other organs.
How: Keeping oxygen saturation in a safe range avoids both low oxygen (which can trigger harmful vessel regrowth) and high oxygen (which can drive abnormal vessels). Large trials showed that lower targets reduce ROP but raise death risk, while higher targets lower death risk but can increase ROP. Units therefore use protocolized, carefully monitored targets (often around low-to-mid 90s) and avoid swings. New England Journal of Medicine+2New England Journal of Medicine+2
Avoiding oxygen “spikes” and “dips”
Purpose: Prevent retinal stress from constant up-and-down oxygen levels.
How: Use alarm limits, gentle titration, closed-loop or protocolized adjustments, and staff training to keep saturations steady. Evidence across the oxygen trials shows fluctuation matters; stability is a practical target derived from those findings. PubMed
Early, guideline-based ROP screening
Purpose: Catch disease at the treatable time.
How: NICUs follow the American Academy of Pediatrics policy (updated 2018) for which babies to screen, when to start (commonly by 31 weeks post-menstrual age or 4 weeks after birth, whichever is later), and how often to recheck until the retina finishes vascularizing or treatment is given. PubMed
Telemedicine wide-field retinal imaging (where appropriate)
Purpose: Expand access and consistency in grading images.
How: Trained imagers capture standardized photos; expert readers grade them remotely to identify “referral-warranted ROP.” The e-ROP projects validated this approach as accurate for detecting babies who need an exam or treatment. PMCJAMA Network
Laser photocoagulation of avascular retina
Purpose: Standard non-drug treatment for type 1 ROP—stops abnormal vessel drive.
How: Laser ablates (shuts down) the peripheral retina that is sending strong growth signals (VEGF), which reduces pathologic neovascularization. Early treatment improves outcomes (ETROP era). Johns Hopkins Medicine
Cryotherapy (when laser unavailable)
Purpose: Older method to destroy peripheral retina when lasers aren’t accessible.
How: Freezing the avascular retina reduces abnormal vessel growth. Still relevant in resource-limited settings, though laser is preferred where available. (Historic CRYO-ROP data underpin this.) Johns Hopkins Medicine
Human milk feeding (prefer maternal milk, adequately fortified)
Purpose: Lower risk of ROP and severe ROP while improving overall outcomes.
How: Human milk provides bioactive factors, antioxidant/anti-inflammatory molecules, and better nutrient balance. Meta-analyses show a protective association against ROP/severe ROP; adequate volume and fortification matter. PediatricsPubMed
Adequate arachidonic acid (AA) and DHA in nutrition
Purpose: Support normal retinal and brain development and may reduce severe ROP.
How: Very preterm infants rapidly become deficient in AA/DHA after birth. Trials and reviews suggest AA+DHA support vascular development; programs are moving toward ensuring better intake (enteral or formula with appropriate LCPUFAs). CochraneNature
Strict infection prevention & control
Purpose: Reduce systemic inflammation that can worsen ROP.
How: Bundles for hand hygiene, line care, antibiotics stewardship, and early recognition of sepsis lower inflammatory hits that can push disease. Review papers emphasize modifiable risks. PMC
Thermoregulation and gentle handling
Purpose: Keep babies warm and calm to lower metabolic stress and oxygen needs.
How: Warm delivery rooms, plastic wraps, humidified incubators, minimal handling, and pain control stabilize physiology—indirectly protecting eyes.
Kangaroo Mother Care (skin-to-skin)
Purpose: Improve physiologic stability, breastfeeding rates, and reduce infections.
How: Skin-to-skin contact helps temperature, breathing patterns, and bonding; by improving stability and milk success, it may indirectly reduce ROP drivers.
Gentle respiratory strategies (CPAP/non-invasive where feasible)
Purpose: Lower oxygen swings and baro/volutrauma.
How: Favoring less invasive ventilation (when safe) may reduce large oxygen requirement swings that stress retinal development.
Protocolized transfusion & anemia management
Purpose: Avoid unnecessary transfusions and hypoxia—both can influence ROP risk.
How: Use evidence-based hemoglobin thresholds and slow, careful transfusion practices to maintain stable oxygen delivery.
Optimize glucose control
Purpose: Hyperglycemia is linked with microvascular stress.
How: Avoid sustained high glucose with careful nutrition/insulin protocols.
Early adequate protein–energy intake (with fortifiers)
Purpose: Promote steady growth and better postnatal weight gain, which correlates with lower ROP risk and underlies prediction tools (e.g., WINROP—helpful but not sufficient alone). PMCNature
Staff education, alarms, and checklists for ROP prevention
Purpose: Drive consistency in oxygen titration, screening timing, and follow-up.
How: Unit-wide protocols reduce missed screens and reduce oxygen instability.
Standardized analgesia for procedures
Purpose: Minimize pain-related desaturations and stress during eye exams and laser.
How: Use safe, neonatal-appropriate comfort measures and medications per NICU policy.
Integrated screening logistics (bedside imaging, shared calendars)
Purpose: Prevent missed/late exams.
How: Multidisciplinary scheduling between NICU, ophthalmology, and imaging teams prevents delays that could push disease past the treatment window. PubMed
Tele-ROP networks for outreach NICUs
Purpose: Provide remote grading where specialists are scarce.
How: Regional programs modeled on e-ROP allow earlier identification and referral. PMC
Early post-discharge ophthalmology follow-up
Purpose: Detect late recurrence after anti-VEGF therapy or continued maturation needs.
How: Set follow-up dates before discharge; late recurrences are recognized risk after anti-VEGF and require prolonged surveillance. PubMed

Drug Treatments

Important safety note: Medication type, dose, timing, and later follow-up for preterm infants are highly specialized. The following is general information only; all dosing is determined by the treating ophthalmologist/neonatologist.

Bevacizumab (anti-VEGF; intravitreal)
Class/Mechanism: Monoclonal antibody against VEGF—curbs abnormal vessel growth.
Typical use/time: One tiny intravitreal injection per eye for treatment-threshold disease (often zone I/type 1 or aggressive posterior ROP).
Purpose: Rapidly regress neovascularization; may preserve peripheral retina compared to laser.
Key evidence: BEAT-ROP found lower recurrence than laser in zone I disease; benefits in zone II were not significant; long-term systemic safety and late recurrence require careful follow-up.
Cautions/side effects: Ocular infection (rare), cataract (rare), potential systemic VEGF suppression (unknown long-term effects), late recurrence months after injection—hence prolonged surveillance. New England Journal of MedicinePubMed
Ranibizumab (anti-VEGF; intravitreal)
Class/Mechanism: Anti-VEGF Fab fragment with lower systemic exposure than bevacizumab.
Typical dose used in trials: 0.2 mg per eye in RAINBOW.
Purpose: Treat type 1 ROP; may have less high myopia at 2 years vs laser.
Key evidence: RAINBOW suggested 0.2 mg ranibizumab might be superior to laser for treatment success, with acceptable safety through 24 weeks and supportive 2-year outcomes.
Cautions: Requires scheduled re-exams for reactivation; off-label or label-specific details vary by region—follow local approvals. PubMed+1
Aflibercept (anti-VEGF; intravitreal)
Class/Mechanism: VEGF trap (binds VEGF-A, VEGF-B, PlGF).
Typical label dose: 0.4 mg intravitreal per eye (per US label approval for ROP).
Purpose: Alternative anti-VEGF for treatment-threshold ROP.
Evidence/Regulatory: FDA approved for ROP (2023) with 0.4 mg dosing information.
Cautions: As with all anti-VEGF in preterms—require long surveillance for recurrence; monitor systemic risks. AAOScienceDirect
Mydriatic eye drops (e.g., phenylephrine, cyclopentolate) – for exams/procedures
Class: Sympathomimetic and anticholinergic.
Purpose: Safely dilate pupils for reliable screening and laser.
Mechanism: Temporarily widens pupil by acting on iris muscles.
Cautions: Systemic absorption can affect heart rate/blood pressure; neonatal-specific protocols and minimal dosing are used.
Topical anesthetic (e.g., proparacaine) – for exams/injections
Purpose: Reduce pain during imaging or injection.
Mechanism: Numbs the surface of the eye.
Cautions: Excess dosing avoided; monitoring for apnea/bradycardia continues.
Antisepsis agents (e.g., povidone-iodine)
Purpose: Prevent endophthalmitis with intravitreal injections.
Mechanism: Rapid broad antiseptic action on ocular surface.
Cautions: Iodine sensitivity is rare; dosing is topical as per ophthalmic standard.
Caffeine citrate (systemic NICU medication)
Class/Mechanism: Adenosine receptor antagonist—stabilizes breathing and lowers apnea events.
Purpose (ROP-related): By reducing apnea and oxygen variability, caffeine is associated with lower severe ROP in some cohorts; it is not a direct eye drug but part of supportive care.
Cautions: Dose is individualized; monitor heart rate and feeding tolerance. Frontiers
Vitamin A (systemic supplementation, NICU protocol-dependent)
Class/Mechanism: Retinoid—supports epithelial integrity, immune function, and retinal development.
Purpose (ROP-related): Meta-analyses suggest reduced any-stage ROP (not consistently severe ROP); practice varies.
Cautions: Dosing schedules are NICU-specific; do not self-supplement. Renaissance School of Medicine
Analgesia/sedation (per NICU protocol) for laser or injections
Purpose: Minimize physiologic stress, desaturation, and pain.
Mechanism/Cautions: Medication choices are individualized to GA/weight with close cardiorespiratory monitoring.
Antibiotic eye drops (selective, post-procedure per ophthalmologist)
Purpose: Some clinicians use short courses after injections; others rely on antisepsis alone—protocols vary.
Cautions: Avoid unnecessary antibiotics; follow ophthalmologist’s orders.

Why anti-VEGF drugs dominate the “drug” list: Medications that directly treat ROP are primarily anti-VEGF injections. Other medicines above support safe exams/procedures or overall stability; they are part of comprehensive care rather than direct anti-ROP pharmacotherapy.

Dietary “Molecular” Supplements

Critical note: Preterm nutrition is prescription-level. Do not start or change any supplement without the NICU team.

Docosahexaenoic Acid (DHA)
Typical NICU approach: Provided via fortified human milk or DHA-containing preterm formulas; research regimens often ~50 mg/kg/day (study-dependent).
Function: Structural omega-3 for retinal photoreceptors.
Mechanism: Supports normal vessel and neural development; may reduce severe ROP when combined with AA. Cochrane
Arachidonic Acid (AA)
Typical approach: Ensure AA intake alongside DHA to maintain balance.
Function: Omega-6 essential for growth; too little AA may impair normal vascular development.
Mechanism: Works with DHA to normalize angiogenic signaling in the developing retina. Nature
Combined AA + DHA
Approach: Balanced provision in milk/fortifier/formula; combined strategies show more consistent benefit than DHA alone.
Function/Mechanism: Restores fetal-like LCPUFA supply after preterm birth. Cochrane
Vitamin A (Retinol/Retinyl palmitate)
Dose: NICU-protocol (e.g., scheduled IM doses) or fortified feeds.
Function: Supports epithelial/retinal maturation.
Mechanism: Retinoid signaling modulates vascular and neural retina development. Renaissance School of Medicine
Vitamin E (α-tocopherol) – not routine high-dose
Function: Antioxidant.
Mechanism: Scavenges free radicals.
Safety: Historic high-dose trials linked to increased sepsis/NEC; not routinely recommended in high doses for ROP prevention today. Nature
Lutein/Zeaxanthin (carotenoids) – investigational
Function: Macular antioxidants.
Mechanism: May improve retinal antioxidant capacity; human infant data are mixed; dosing is not standardized for ROP prevention. ScienceDirect
Zinc
Function: Cofactor for enzymes, retinal function.
Mechanism: Supports growth and immunity; effect on ROP is uncertain; dosing follows general preterm nutrition guidelines. Nature
Iron (enteral, later in course per NICU)
Function: Prevent/treat anemia, support growth.
Mechanism: Improves oxygen delivery; ROP-specific effects not proven; dosing is standardized in NICU protocols.
Human-milk fortifier (multi-nutrient)
Function: Adds protein, minerals, and micronutrients to expressed milk to meet preterm needs.
Mechanism: Better growth and steady weight gain—an indirect protective factor for ROP risk models. PMC
Choline/taurine (via fortifiers/formulas)
Function: Support retinal and brain development.
Mechanism: Structural and neurotransmission roles; ROP-specific benefits not established—used as part of complete preterm nutrition.

Regenerative / Stem-cell” Drugs

Please read carefully: None of the following are approved treatments for ROP. They are discussed because families ask about “immunity boosters” and “regenerative” options. Your team may use some for general neonatal health, while others are research-only.

Bovine lactoferrin (enteral)
Function: Antimicrobial/immune-modulating milk protein.
Mechanism: Binds iron, reduces pathogen growth, supports gut barrier—used in some NICUs to reduce late-onset sepsis; no direct ROP indication. Dosing is NICU-specific.
Probiotics (specific strains; enteral)
Function: Support gut microbiome, reduce necrotizing enterocolitis.
Mechanism: Colonization resistance and immune modulation; ROP effect uncertain. Use only if your NICU protocol includes them.
Palivizumab (monoclonal antibody against RSV; injections during RSV season)
Function: Prevent severe RSV disease in high-risk infants.
Mechanism: Passive immunity; helps avoid respiratory instability and hypoxia that could destabilize oxygen control; not a ROP drug.
IGF-1/IGFBP-3 replacement (investigational)
Function: Replace low postnatal IGF-1 to support vascular/organ development.
Mechanism: IGF-1 is crucial for physiologic retinal angiogenesis; trials are ongoing; not standard care for ROP. Nature
Mesenchymal stem cell–derived therapies (research-only)
Function/Mechanism: Experimental paracrine support (exosomes, trophic factors) in animal OIR models; no approved neonatal ROP use; no dosing outside trials.
Autologous cord blood–derived cells (research-only)
Function/Mechanism: Investigational regenerative approaches; not approved for ROP; discuss only within formal clinical trials.

Bottom line: These are not ROP treatments. They target infection reduction or are experimental. Decisions belong strictly to the neonatology/ophthalmology team and ethics-approved trials.

Procedures / Surgeries

Laser photocoagulation (standard of care for many cases)
What it is: Using a laser to treat the peripheral avascular retina.
Why it’s done: Stops the retina from sending intense growth signals that drive abnormal vessels; reduces risk of detachment. Early treatment improved outcomes in the ETROP era. Johns Hopkins Medicine
Intravitreal anti-VEGF injection (office/bedside procedure)
What it is: Tiny injection of anti-VEGF into the eye.
Why: Regresses neovascularization quickly, often preserves more retina than laser; requires longer follow-up due to late reactivations. Evidence includes BEAT-ROP (bevacizumab) and RAINBOW (ranibizumab). PubMed+1
Lens-sparing pars plana vitrectomy (LSV)
What it is: Micro-incision surgery to remove tractional membranes and vitreous scaffolding in stage 4 retinal detachment, keeping the lens in place when possible.
Why: Relieves traction to reattach the retina and preserve vision potential. Multiple series show good anatomic success for stage 4A; outcomes are harder in 4B/5. PMCJAMA Network
Scleral buckle (SB)
What it is: A silicone band around the eye to counter traction on the retina in selected detachments (usually 4A/4B).
Why: Provides external support; chosen case-by-case and sometimes combined with vitrectomy. Evidence shows variable success; stage 4A does better than later stages. canadianjournalofophthalmology.caPubMed
Lensectomy with vitrectomy (for advanced stage 5 or cataract after earlier surgery)
What it is: Removing the lens plus vitrectomy when access is limited or lens is opacified.
Why: Attempt to reattach totally detached retina or manage post-treatment cataract; outcomes are guarded in stage 5. PMC

Practical Prevention Steps

Follow AAP screening schedules exactly and keep every appointment. PubMed
Keep oxygen saturations in the unit’s target range and avoid rapid changes. New England Journal of Medicine+1
Human milk nutrition with appropriate fortification for growth. Pediatrics
Ensure adequate AA + DHA intake under NICU guidance. Cochrane
Prevent and promptly treat infections with strict NICU hygiene. PMC
Use gentle respiratory strategies and avoid oxygen spikes/dips. PubMed
Maintain thermal stability and minimize stress/pain.
Follow transfusion and glucose protocols to avoid extremes.
Use tele-ROP imaging networks if access to specialists is limited. PMC
Arrange long-term follow-up after treatment, especially after anti-VEGF. PubMed

When to See Doctors

All eligible preterm infants should enter a screening program by about 31 weeks post-menstrual age or 4 weeks after birth (whichever is later), then be re-examined every 1–3 weeks until the retina has safely matured or treatment is completed. The NICU team schedules this before discharge. PubMed
Immediate care if parents notice drifting eyes, a white pupil, or a sudden change in visual behavior in an older infant who had ROP—these can signal late complications and need urgent evaluation. National Eye Institute

What to Eat” and “What to Avoid

These apply to the feeding plan for the baby and, when breastfeeding, to the mother’s diet—always guided by your NICU team.

What to eat / include

Mother’s own milk, pumped frequently, with human-milk fortifier as prescribed. Pediatrics
Balanced AA + DHA intake (via fortified milk or specialized preterm formula); mothers can discuss DHA-rich fish (low-mercury) with dieticians. Cochrane
Adequate protein for steady growth (provided by fortifiers/formulas).
Standard preterm micronutrients (iron, zinc, vitamin D) per NICU orders—these support overall growth and immunity; ROP-specific effects vary. Nature
Hydration and frequent feeds to meet calorie goals.

What to avoid / limit

Unsupervised supplements (including high-dose vitamin E) due to safety concerns. Nature
Long gaps between feeds that slow weight gain.
Unpasteurized donor milk unless processed per NICU standards.
High-mercury fish in a breastfeeding mother’s diet (choose low-mercury DHA sources).
Herbal/traditional remedies not cleared by neonatology.

Frequently Asked Questions

Can mild ROP go away by itself?
Yes. Early stages can regress as the retina matures, but only careful screening can tell if it’s safe to watch or if treatment is needed. PubMed
Which is better—laser or injections?
Both are effective when used at the right time. Laser is time-tested and curative for many cases; anti-VEGF injections can be especially helpful in posterior (zone I) disease and may preserve more peripheral retina, but they require longer follow-up for late recurrence. Your specialist chooses based on disease pattern. PubMed+1
Are anti-VEGF injections safe for the whole body?
Eye infections are rare with proper antisepsis. Systemic effects in tiny babies are a key concern; teams use the lowest effective dose and follow babies closely over time. Long-term systemic safety is still being studied. PubMed
Will my baby need glasses later?
Children with ROP—especially those needing treatment—have higher risks of myopia, strabismus, amblyopia, and other issues. Early pediatric ophthalmology follow-up helps manage these. National Eye Institute
How long does follow-up last after injections?
Months to years. Late ROP reactivation can occur after anti-VEGF, so scheduled exams continue even when eyes look quiet. PubMed
Do oxygen targets change as my baby grows?
Units often adjust targets as infants mature, balancing eye and overall outcomes. This is guided by neonatology protocols informed by big trials. New England Journal of Medicine
Does human milk really help?
Meta-analyses associate human milk with lower ROP risk, especially with adequate volume and fortification. It also benefits the gut, immunity, and brain. Pediatrics
Should we give DHA drops?
Never without NICU guidance. Teams usually meet AA/DHA needs through fortified milk or preterm formula; if supplements are used, dose and balance with AA matter. Cochrane
Is vitamin E good for ROP?
High-dose vitamin E is not routine due to sepsis/NEC risks in older studies. Your team will decide on safe micronutrient plans. Nature
What’s tele-ROP?
Wide-field images captured by trained staff are graded remotely by experts to decide who needs an in-person exam—useful where specialists are scarce. PMC
Can surgery restore vision if the retina detaches?
Surgery (vitrectomy, scleral buckle) aims to reattach the retina and improve the chance of useful vision. Success is best in stage 4A and decreases in more advanced stages. PMCPubMed
Will my baby have pain during treatment?
Teams use neonatal-appropriate analgesia and comfort measures for exams, lasers, and injections.
Do we need to change feeding at home?
Follow the NICU nutrition plan and outpatient dietician advice; growth targets are important for eye health too.
Could ROP come back after discharge?
Yes, especially after anti-VEGF—hence scheduled ophthalmology visits even if eyes looked good earlier. PubMed
What’s the single most important thing we can do?
Don’t miss screenings or follow-ups and keep oxygen stable within your unit’s target range—these two steps save sight. PubMedNew England Journal of Medicine

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: August 24, 2025.

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