Foveal Hypoplasia in Retinopathy of Prematurity (ROP)
• Definition and Pathophysiology:
• Foveal hypoplasia (FH) is characterized by a shallow or absent foveal depression due to abnormal foveal development.
• Normal foveal development begins at 22 weeks gestation and completes by 13 years of age.
• Key histological features of foveal maturation include centrifugal displacement of inner retinal layers, cone photoreceptor specialization, and centripetal migration of cone photoreceptors.
• In preterm infants, FH is associated with increased foveal thickness and shallow foveal depressions observed on optical coherence tomography (OCT).
• Study Overview:
• Cross-sectional study evaluating foveal development in 166 eyes from 83 patients with a history of ROP.
• Compared foveal development between spontaneous regression and treated eyes (laser photocoagulation [LPC] or intravitreal anti-vascular endothelial growth factor [anti-VEGF, bevacizumab]).
• Used OCT with Thomas et al. grading system (modified by Leicester Grading) to assess FH severity.
• Foveal Hypoplasia Grading:
• Grade 0: Normal foveal development (V-shaped pit, outer segment lengthening, outer nuclear layer [ONL] widening).
• Grade 1a: V-shaped pit with outer segment lengthening and ONL widening.
• Grade 1b: Shallow indents with similar outer segment and ONL changes.
• Grade 2: Grade 1 features without a discernible pit.
• Grade 3: Grade 2 features without outer segment lengthening.
• Grade 4 (fovea plana): Grade 3 features without ONL widening (not observed in this study).
• Atypical FH: Shallow pit with hyporeflective zone due to inner segment ellipsoid band disruption (not observed).
• Key Findings:
• Foveal development significantly differed between treatment (LPC or anti-VEGF) and spontaneous regression groups (P=0.000).
• FH was more severe in treated eyes compared to spontaneous regression eyes.
• Prevalence of normal foveal development (Grade 0):
• Spontaneous regression: 67.2%
• LPC: 34.2%
• Anti-VEGF: 40%
• Factors correlating with FH severity:
• Lower gestational age (GA) (P=0.000, rho=-0.474).
• Lower birth weight (P=0.000, rho=-0.406).
• Younger postmenstrual age at treatment (P=0.04, rho=-0.362).
• Higher ROP stage (P=0.002, rho=0.242).
• More posterior ROP zone (P=0.009, rho=-0.203).
• Visual acuity outcomes:
• Mild FH (Grades 0-2) did not significantly affect visual acuity; 88.5% of patients had logMAR 0.
• Only one patient with Grade 3 FH had reduced visual acuity (logMAR 0.8).
• No patients developed strabismus.
• Clinical Implications:
• ROP treatment (LPC or anti-VEGF) may induce morphological alterations in foveal development, potentially due to treatment itself or as a marker of more severe disease.
• Early-stage foveal development is not significantly disrupted in ROP, unlike congenital disorders (e.g., albinism, aniridia), leading to fewer severe structural abnormalities.
• FH in ROP is primarily influenced by environmental factors (prematurity, treatment) rather than genetic factors, unlike in full-term infants.
• No significant difference in FH severity between LPC and anti-VEGF groups, suggesting treatment timing (31-42 weeks gestation) is critical.
• Study Limitations:
• Limited sample size relative to ROP incidence.
• FH grading system designed for congenital disorders, not ROP-specific.
• Cross-sectional design lacked longitudinal monitoring of foveal development.
• Did not evaluate postnatal environmental factors (e.g., blood transfusion, sepsis) or histopathological analysis.
• Prognostic and Diagnostic Notes:
• OCT is critical for evaluating foveal development in ROP patients.
• FH severity correlates with ROP severity (stage and zone), guiding prognosis.
• Severe FH (Grades 3-4) is rare in ROP, explaining minimal visual impairment in most cases.
### Citation
Çelik G, Oto BB, Kızılary O, Günay M. Evaluation of foveal hypoplasia in children with a history of retinopathy of prematurity. *Retina*. 2025;45:660-666. doi:10.1097/IAE.0000000000004103
• Foveal hypoplasia (FH) is characterized by a shallow or absent foveal depression due to abnormal foveal development.
• Normal foveal development begins at 22 weeks gestation and completes by 13 years of age.
• Key histological features of foveal maturation include centrifugal displacement of inner retinal layers, cone photoreceptor specialization, and centripetal migration of cone photoreceptors.
• In preterm infants, FH is associated with increased foveal thickness and shallow foveal depressions observed on optical coherence tomography (OCT).
• Study Overview:
• Cross-sectional study evaluating foveal development in 166 eyes from 83 patients with a history of ROP.
• Compared foveal development between spontaneous regression and treated eyes (laser photocoagulation [LPC] or intravitreal anti-vascular endothelial growth factor [anti-VEGF, bevacizumab]).
• Used OCT with Thomas et al. grading system (modified by Leicester Grading) to assess FH severity.
• Foveal Hypoplasia Grading:
• Grade 0: Normal foveal development (V-shaped pit, outer segment lengthening, outer nuclear layer [ONL] widening).
• Grade 1a: V-shaped pit with outer segment lengthening and ONL widening.
• Grade 1b: Shallow indents with similar outer segment and ONL changes.
• Grade 2: Grade 1 features without a discernible pit.
• Grade 3: Grade 2 features without outer segment lengthening.
• Grade 4 (fovea plana): Grade 3 features without ONL widening (not observed in this study).
• Atypical FH: Shallow pit with hyporeflective zone due to inner segment ellipsoid band disruption (not observed).
• Key Findings:
• Foveal development significantly differed between treatment (LPC or anti-VEGF) and spontaneous regression groups (P=0.000).
• FH was more severe in treated eyes compared to spontaneous regression eyes.
• Prevalence of normal foveal development (Grade 0):
• Spontaneous regression: 67.2%
• LPC: 34.2%
• Anti-VEGF: 40%
• Factors correlating with FH severity:
• Lower gestational age (GA) (P=0.000, rho=-0.474).
• Lower birth weight (P=0.000, rho=-0.406).
• Younger postmenstrual age at treatment (P=0.04, rho=-0.362).
• Higher ROP stage (P=0.002, rho=0.242).
• More posterior ROP zone (P=0.009, rho=-0.203).
• Visual acuity outcomes:
• Mild FH (Grades 0-2) did not significantly affect visual acuity; 88.5% of patients had logMAR 0.
• Only one patient with Grade 3 FH had reduced visual acuity (logMAR 0.8).
• No patients developed strabismus.
• Clinical Implications:
• ROP treatment (LPC or anti-VEGF) may induce morphological alterations in foveal development, potentially due to treatment itself or as a marker of more severe disease.
• Early-stage foveal development is not significantly disrupted in ROP, unlike congenital disorders (e.g., albinism, aniridia), leading to fewer severe structural abnormalities.
• FH in ROP is primarily influenced by environmental factors (prematurity, treatment) rather than genetic factors, unlike in full-term infants.
• No significant difference in FH severity between LPC and anti-VEGF groups, suggesting treatment timing (31-42 weeks gestation) is critical.
• Study Limitations:
• Limited sample size relative to ROP incidence.
• FH grading system designed for congenital disorders, not ROP-specific.
• Cross-sectional design lacked longitudinal monitoring of foveal development.
• Did not evaluate postnatal environmental factors (e.g., blood transfusion, sepsis) or histopathological analysis.
• Prognostic and Diagnostic Notes:
• OCT is critical for evaluating foveal development in ROP patients.
• FH severity correlates with ROP severity (stage and zone), guiding prognosis.
• Severe FH (Grades 3-4) is rare in ROP, explaining minimal visual impairment in most cases.
### Citation
Çelik G, Oto BB, Kızılary O, Günay M. Evaluation of foveal hypoplasia in children with a history of retinopathy of prematurity. *Retina*. 2025;45:660-666. doi:10.1097/IAE.0000000000004103
