Introduction: Retinopathy of Prematurity Clinical Trials
Definition of Retinopathy of Prematurity
Retinopathy of prematurity (ROP) is a retinal disease that can develop in premature babies born before 31 weeks of pregnancy (a full-term pregnancy is about 38 to 42 weeks) or who weigh less than 3 pounds at birth. It is one of the leading causes of preventable childhood blindness, and its incidence is increasing with the increase in the survival of preterm babies.
Causes of Retinopathy of Prematurity
Multiple causative factors are involved in the development of ROP. It occurs when there is an abnormal growth of vessels in the retina (the light-sensitive part of the eye). As the preterm baby is delivered and supplemental oxygen is given, the normal development of vessels of the retina is arrested, leading to hypoxia (lack of oxygen). This hypoxia, in turn, stimulates the production of vascular growth factors leading to abnormal vascularization of the retina. This can cause fibrous scarring and even retinal detachment leading to blindness in children.
Management of Retinopathy of Prematurity
For the management of this severe disease and its comorbidities, the numerous factors involved in its development should be identified and controlled. The management strategies should be synergistic and complementary, involving controlled supplemental oxygen therapy, nutritional optimization and growth evaluation, breastfeeding, and control of hyperglycemic episodes associated with prematurity.
Stages of Retinopathy of Prematurity
ROP is divided into five stages depending on the severity, and the treatment is done according to it. This classification is as follows:
Stage 1: This is the initial stage in which there is a clear-cut whitish demarcation line between the normal retina and the avascular area of the retina.
Stage 2: In this stage, the whitish demarcating line develops into a ridge having a height and width between the normal and avascular retina.
Stage 3: This stage involves the growth of blood vessels in the ridge showing the visible proliferation of new vessels.
Stage 4: This includes sub-total retinal detachment caused by proliferating vessels.
Stage 5: This stage is characterized by total retinal detachment.
Stages 1 and 2 usually do not need treatment, and the patients get better with time. However, careful and regular examination may be needed for some time. Stage 3 may also get better without any treatment but sometimes need treatment if there is a progression of the disease. Stage 4 has a partially detached retina and usually needs surgery. Stage 5 is not treatable in most conditions as total detachment has occurred already.
Clinical Trials for Retinopathy of Prematurity
Numerous studies are being conducted on ROP to find new treatment techniques in order to save children from blindness. Some of these clinical trials are being discussed here as follows:
Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity
It was observed that preterm babies born before 31 weeks of pregnancy miss the transfer from the mother to the child of arachidonic acid (AA), a ω-6 long-chain polyunsaturated fatty acid (LCPUFA), and docosahexaenoic acid (DHA), a ω-3 long-chain polyunsaturated fatty acid (LCPUFA). These lipids play a significant role in the development of the retina and brain, and their deficiency is associated with vascular complications in preterm babies.
Preterm babies suffer from the deficiency of these vital long-chain fatty acids as breast milk does not contain sufficient amounts of arachidonic acid (AA) and docosahexaenoic acid (DHA), nor does the parenteral fluids which are given during hospital stay. This may be one of the contributing factors in the development of retinopathy of prematurity (ROP).
Due to this reason, research is being done to check the role of enteral (per oral) lipid supplementation in preterm babies in order to decrease the severity and incidence of ROP.
In this study, two groups of infants were evaluated. One was given supplementation with AA (100mg/kg/d) and DHA (50 mg/kg/d) in the form of enteral oil, and the other received no supplementation within 3 days after birth until postmenstrual age of 40 weeks.
- Study type – Interventional
- Enrollment – 210 participants
- Allocation – Randomized
- Primary purpose – Prevention
Ranibizumab in retinopathy of prematurity – one-year follow-up of ophthalmic outcomes and two-year follow-up of neurodevelopmental outcomes from the CARE-ROP study
Vascular endothelial growth factors (VEGF) produced as a result of retinal hypoxia (lack of oxygen) are considered one of the culprits leading to the vasoproliferation and development of ROP. In order to prevent this, anti-VEGF medications are being used, such as ranibizumab, bevacizumab, and aflibercept.
This study focuses on the long-term effects of ranibizumab, an anti-VEGF drug, regarding outcomes of ophthalmic (related to the eye) conditions and neurodevelopmental outcomes.
In this study, the effect of 0.12 mg versus 0.20 mg ranibizumab in 20 infants with retinopathy of prematurity (ROP) was compared in a randomized, double-blind, controlled study design.
- Study type – Interventional
- Enrollment – 20 participants
- Allocation – Randomized
- Primary purpose – Treatment
Effects of Early Vitamin A Supplementation on the Risk for Retinopathy of Prematurity in Extremely Preterm Infants
Vitamin A is a significant micronutrient for normal eye functions as it is needed for the formation of retinaldehyde and rhodopsin, which as essential for normal visual functions. The retinal rhodopsin levels increase with the increase in gestational age, reaching almost seven-fold during the third trimester. This increase in rhodopsin level is dependent upon the sufficiency of vitamin A in the body.
Most of vitamin A is stored in the liver. But hepatic storage of vitamin A in a preterm baby is not enough because of reduced transfer of vitamin A from mothers in case of prematurity. In such cases, vitamin A supplementation may prove helpful in preventing retinopathy of prematurity (ROP).
In this study, 262 preterm infants were included. Almost half of them (i.e., 132 infants) were given vitamin A supplementation (1,500 IU/day) in addition to their oral feed, while the other 130 were given no supplementation. This supplementation was continued for 28 days or until discharge of the preterm infants, and results were followed.
- Study type – Interventional
- Enrollment – 262 participants
- Allocation – Randomized
- Primary purpose – Prevention
Mother Milk as an Eye Drop & Premature Retinopathy
In many areas of the world, breast milk is used as an eye drop in to clean eyes, especially in infants, as it is considered that breast milk treats and prevents eye infections and discharge. Breast milk contains different beneficial components such as immunoglobulins, immune cell subsets, lactoferrin, lysozyme, and oligosaccharides.
In this study, the breast milk of an infant’s own mother was instilled into the eyes as eye drops in a randomized controlled study to check its efficacy and role in the prevention of retinopathy of prematurity.
After the randomization of 101 infants, two groups were made. 0.5 ml of breast milk from the infant’s own mother was instilled into the eye of the intervention group. While in the control group, 0.9% normal saline was instilled into the eyes of infants of the other group. Both groups were then followed for the outcome.
- Study type – Interventional
- Enrollment – 101 participants
- Allocation – Randomized
- Primary purpose – Prevention
Conclusion
Various research and clinical trials are being conducted in order to study the disease and improve the outcome of the disease. By participating in the clinical trials, you can play your role in the effort to prevent and manage the retinopathy of prematurity in the future.
See Also
Win Ratio DIAMOND Clinical Trial
Microdosing Mushroom Clinical Trials
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Sources
- Hellström A, Smith LE, Dammann O. Retinopathy of prematurity. Lancet. 2013 Oct 26;382(9902):1445-57. doi: 10.1016/S0140-6736(13)60178-6. Epub 2013 Jun 17. PMID: 23782686; PMCID: PMC4389630.
- Brown AC, Nwanyanwu K. Retinopathy Of Prematurity. 2022 Sep 5. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 32965990.
- Bashinsky AL. Retinopathy of Prematurity. N C Med J. 2017 Mar-Apr;78(2):124-128. doi: 10.18043/ncm.78.2.124. PMID: 28420777.
- Hellström A, Nilsson AK, Wackernagel D, Pivodic A, Vanpee M, Sjöbom U, Hellgren G, Hallberg B, Domellöf M, Klevebro S, Hellström W, Andersson M, Lund AM, Löfqvist C, Elfvin A, Sävman K, Hansen-Pupp I, Hård AL, Smith LEH, Ley D. Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity: A Randomized Clinical Trial. JAMA Pediatr. 2021 Apr 1;175(4):359-367. doi: 10.1001/jamapediatrics.2020.5653. PMID: 33523106; PMCID: PMC7851754.
- Stahl A, Bründer MC, Lagrèze WA, Molnár FE, Barth T, Eter N, Guthoff R, Krohne TU, Pfeil JM; CARE-ROP Study Group. Ranibizumab in retinopathy of prematurity – one-year follow-up of ophthalmic outcomes and two-year follow-up of neurodevelopmental outcomes from the CARE-ROP study. Acta Ophthalmol. 2022 Feb;100(1):e91-e99. doi: 10.1111/aos.14852. Epub 2021 Mar 19. PMID: 33742551; PMCID: PMC9460412.
- Sun H, Cheng R, Wang Z. EARLY VITAMIN A SUPPLEMENTATION IMPROVES THE OUTCOME OF RETINOPATHY OF PREMATURITY IN EXTREMELY PRETERM INFANTS. Retina. 2020 Jun;40(6):1176-1184. doi: 10.1097/IAE.0000000000002543. PMID: 30964778; PMCID: PMC7242171.
- Mother Milk as a Eye Drop & Premature Retinopathy – Full Text View – ClinicalTrials.gov. (n.d.). Mother Milk as a Eye Drop & Premature Retinopathy – Full Text View – ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT04883931
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