The Prevalence of Foveal Hypoplasia in Inherited Retinal Diseases
Kellogg Eye Center, Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, 1000 Wall St, Ann Arbor, MI 48105, USA
*
Author to whom correspondence should be addressed.
J. Clin. Transl. Ophthalmol. 2025, 3(3), 11; https://doi.org/10.3390/jcto3030011
Submission received: 9 January 2025
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Revised: 29 April 2025
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Accepted: 24 June 2025
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Published: 26 June 2025
Abstract
Background: The prevalence of foveal hypoplasia in different inherited retinal diseases (IRDs) has not been compared in a large patient cohort. We aimed to investigate the prevalence and visual significance of foveal hypoplasia in IRDs. Methods: Participants included patients with IRDs and control subjects. All patients had macular optical coherence tomography (OCT). Results: Among our 357 patients, 123 had rod-cone dystrophy (34.5%), 22 had cone/cone-rod dystrophy (6.2%), 30 had macular dystrophy (8.4%), and 182 (51%) were controls. Having a phenotype of rod-cone (OR = 12.9, p < 0.001) or cone/cone-rod dystrophy (OR = 10.2, p < 0.001) was associated with higher odds of having foveal hypoplasia. Males had higher odds of having foveal hypoplasia (OR = 2.4, p = 0.006). The prevalence of foveal hypoplasia in the retinitis pigmentosa GTPase regulator (RPGR) group (8/15 (53.3%)) was significantly higher than in matched controls (0/15, 0.0%) (p = 0.002). Atypical foveal hypoplasia had the highest LogMAR of 0.50 (±0.37), which was higher than grade one 0.16 (±0.17) (p = 0.038). Grade one LogMAR was not different from normal fovea 0.20 (±0.28) (p = 0.572). Conclusions: We report that rod-cone and cone/cone-rod IRDs are associated with foveal hypoplasia. Based on our findings, detection of foveal hypoplasia in a patient with reduced vision should prompt consideration of an IRD.
1. Introduction
Foveal hypoplasia (foveal hypoplasia) is a congenital variation resulting from disruption of normal development of the human fovea. Developmental arrest (i.e., foveal hypoplasia) during the foveal development leads to persistence of inner retinal layers, with a shallow or absent foveal pit, persistence of outer nuclear layer widening, and presence of photoreceptor outer segment lengthening [1]. Inherited retinal diseases (IRDs) are genetic conditions that can affect different parts of the retina including the fovea. Given the diversity of IRDs and the distinct forms of vision loss they cause, it would be of importance to analyze which forms of IRDs are associated the most with development of foveal hypoplasia as that can increase our understanding of factors involved in the foveal developmental pathway.
Prevalence of foveal hypoplasia has been reported in certain IRDs, such as ocular and oculocutaneous albinism, achromatopsia [2,3,4], disorders of ocular development associated with PAX6 mutations, and C31B-associated dystrophy [5], but foveal hypoplasia has not been reported in rod-cone and cone-rod dystrophies or compared between different types of IRDs. Furthermore, a number of previous studies [3,5] included patients with ages below the time point that marks complete foveal development (45 months) [1]. This could confuse foveal hypoplasia with normal foveal development per the specified age.
The visual significance of foveal hypoplasia has been investigated previously. Foveal hypoplasia causes a significant decrease in BCVA proportional to the hypoplasia’s grade [1]. However, the visual significance of the mildest form of foveal hypoplasia (grade one) is still of debate, as some papers show a decrease in visual acuity while others do not [4,6,7]. Given the presence of outer nuclear layer widening and photoreceptor outer segment lengthening despite under-development of the foveal pit in foveal hypoplasia grade one, cone specialization may still occur normally and grade one foveae may have full visual functionality in the absence of foveal cone degeneration [7].
In this study, we aim to (1) broadly investigate the association of different factors with the prevalence of foveal hypoplasia such as IRD phenotype, gender, and age, (2) examine the prevalence of foveal hypoplasia amongst some of the most common IRD genotypes, and (3) investigate the effect of foveal hypoplasia on visual acuity.
2. Materials and Methods
This is a case-series study which was conducted at University of Michigan’s Kellogg Eye Center. It adhered to the tenets of the Declaration of Helsinki and the regulations of the Health Insurance Portability and Accountability Act. Institutional Review Board approval was obtained (HUM00028413), informed consent was waved as this study is considered a secondary analysis of a pre-existing dataset (retrospective chart review study). Data were obtained through a chart review of patients seen between 15 August 2012 and 24 July 2019. Participants belonged to two groups: IRD and control groups. For the IRD group, the inclusion criteria were (1) having a clinical diagnosis of an IRD (rod-cone, cone/cone-rod, or macular dystrophy) [8] based on a combination of clinical history, examination, electroretinography, pedigree analysis, Goldmann visual field testing, optical coherence tomography, and fundus autofluorescence, and (2) having a conclusive genetic diagnosis of IRD obtained through testing with a Clinical Laboratory Improvement Amendments certified laboratory. The control group included subjects without an IRD diagnosis seen at the Kellogg Eye Center who had OCT. The control group included subjects with diagnoses of non-proliferative diabetic retinopathy, peripheral choroidal nevus, uveitis, glaucoma suspects, central serous retinopathy, or screening for hydroxychloroquine maculopathy. All patients (IRD and control) had optical coherence tomography (OCT) imaging (Spectralis OCT; Heidelberg Engineering, Heidelberg, Germany). The imaging protocol consisted of three scans. The first was a 25-line, high speed volume scan with an automatic real-time tracking (ART) of 9 (512 A-scan per line). The second and third scans (1 vertical and 1 horizontal) had 2–7 lines and were high resolution volume, with an ART of 9 (1536 A-scans per line). The foveal light reflex was used as a marker for initial centration followed by manual relocation of the central line to ensure it went through the thinnest part of the macula prior to initiating any scan. Criteria of exclusion in this study were age less than 4 years to ensure that formation of the fovea is physiologically complete [1], poor-quality OCT with poor resolution of retinal layers, and retinal pathology precluding determination of foveal hypoplasia, such as epiretinal membrane, cystoid macular edema, or loss of lamination of all inner retinal layers due to advanced disease, as these pathologies would lead to ambiguity with grading.
Collected data included age, gender, race, ethnicity, IRD phenotype (rod-cone, cone/cone-rod, macular dystrophy), genetic testing results, Snellen monocular best and worst corrected visual acuity, and OCT images. Age, OCT, and visual acuity were collected at a time point after the genetic and phenotypic diagnosis of IRD was confirmed. One grader (RA) who was unaware of the IRD phenotype reviewed the OCT scans. The scans for each eye were reviewed to evaluate the foveal anatomy; then, the anatomy of the fovea was identified either as normal or hypoplastic working using a previously published grading system [1]. All BCVA Snellen values were converted to their logarithm of the minimum angle of resolution (LogMAR). Age, better, and worse eye LogMAR were compared between the control and IRD groups using Welch’s t-test. The chi-square test of independence was used to compare the control and IRD groups for gender, race, ethnicity, and presence of foveal hypoplasia. To study the different factors that can affect foveal anatomy (normal or hypoplastic), a multivariable binary logistic regression model was utilized, with the independent (predictor) variables consisting of age, gender, and patient subgroup (control group, rod-cone, cone/cone-rod, and macular dystrophies). Independent variables were loaded using the stepwise forward conditional method. The analysis was presented per patient; presence of foveal hypoplasia in either eye was considered positive regardless of the grade. If foveal hypoplasia of any grade with the presence of attenuation and/or discontinuation in the ellipsoid zone was present in either eye, the patient was considered as having atypical foveal hypoplasia.
In addition to the multivariable model, we performed a series of univariate analyses to evaluate the effect of each of the main genotypes in our study on the prevalence of foveal hypoplasia. Given how susceptible univariate analysis is to confounding/moderating variables (e.g., gender), each genotype group was matched to the control group based on as many variables as possible (age and gender), producing case-control contingency tables. Age in the control group was matched within 1.96 of the standard error in the genotype group. In each of the case-control contingency tables, the proportion of males and the mean age were not statistically different between cases and controls. Within each contingency table, the genotypes and the matched control group were compared based on the prevalence of foveal hypoplasia by applying Fisher’s exact test.
To study the effect of foveal hypoplasia on central vision, we analyzed the rod-cone dystrophy group, as it was the largest in our cohort. Within the rod-cone phenotype, better and worse eye visual acuities were compared between three groups, patients with normal foveae, grade one, and atypical foveal hypoplasia, using Welch’s ANOVA followed by Games–Howell post-hoc testing [9]. All statistical analysis was done using IBM SPSS version 23 (IBM Co., Armonk, NY, USA).
3. Results
The study sample consisted of 357 patients, including 175 IRD cases and 182 controls. Of the 357 patients, 180 (50.4%) were females. The mean age and standard deviation (SD) were 45 and 16.6 years, respectively. Two hundred seventy-eight (77.9%) were White patients, 319 (89.4%) were Non-Hispanic. Demographics were similar between groups except for age, where the control group’s mean (SD) of 52 (13.8) was significantly higher than the IRD group’s (38 (17.1)) (p < 0.001). The age difference between the two groups is not expected to confound results as foveal hypoplasia is a developmental and stationary anatomical feature after the age of 4 years [1]. The phenotypes for the IRD cases were 123 rod-cone dystrophy (70.3%), 22 cone/cone-rod dystrophy (12.6%), and 30 macular dystrophy patients (17.1%). The control group consisted of 182, which is 51% of the overall study sample. The most common (n > 8) genetic causes of disease were mutations in usherin (USH2A) (30, 17.1%), ATP binding cassette subfamily A member 4 (ABCA4) (25, 14.3%), retinitis pigmentosa GTPase regulator (RPGR) (18, 10.3%), and peripherin-2 (PRPH2) (10, 5.7%) genes. The mean (SD) better and worse eye logMAR visual acuities for the control group were 0 (0.1) and 0.0 (0.1), respectively. The mean (SD) better and worse eye LogMAR for the IRD groups were 0.3 (0.3) and 0.4 (0.4), respectively. The IRD group had a mean LogMAR that was significantly higher (worse) than the control group in both better (p < 0.001) and worse (p < 0.001). Based on foveal anatomy, 8 patients (4.4%) from the control and 54 (30.9%) from the IRD group had foveal hypoplasia (Table 1).
When comparing the prevalence of foveal hypoplasia by phenotype, rod-cone (44/123, 35.8%) and cone/cone-rod (8/22, 36.4%) dystrophies had a higher prevalence of foveal hypoplasia compared to macular dystrophy (2/30, 6.7%). The control group had 8/182 patients with foveal hypoplasia (4.4%). When looking at the grades of foveal hypoplasia within each phenotype, rod-cone dystrophy cases were mainly grade one (34/44, 77.3%), while the majority of cone/cone-rod (7/8, 87.5%) and macular dystrophy (2/2, 100%) had the atypical grade due to photoreceptor degeneration. All 8 patients with foveal hypoplasia in the control group were classified as grade one (100%). In regards to visual function, cone/cone-rod dystrophy had the highest median (interquartile range (IQR)) logMAR visual acuities in the better 0.5 (0.2–0.7) and worse 0.7 (0.3–1.0) eyes followed by macular dystrophy (better = 0.3 (0.1–0.5); worse = 0.5 (0.3–0.7)), rod-cone dystrophy (better = 0.1 (0.0–0.3); worse = 0.2 (0.1–0.4)), and, lastly, the control group (better = 0.0 (0.0–0.0); worse = 0.0 (0.0–0.0)) (Table 2). The prevalence of foveal hypoplasia was similar amongst the three most common genetic etiologies: 9/18 (50%) for RPGR, followed by USH2A (7/30, 23.3%), PRPH2 (2/10, 20%), and ABCA4 (2/25, 8.0%). ABCA4 had the highest (worst) LogMAR with a better and worse visual acuity of 0.3 (0.1–0.5) and 0.5 (0.3–0.8), respectively. USH2A (better eye = 0.1 (0.0–0.2), worse eye = 0.1 (0.1–0.3)), RPGR (better eye = 0.1 (0.1–0.2), worse eye = 0.2 (0.2–0.6)), and PRPH2 [better eye = 0.1 (0.0–0.5), worse eye = 0.3 (0.2–0.6)) had LogMAR visual acuities that were close in value (Table 3).
Our multivariable analysis showed that having a phenotype of rod-cone (OR = 12.9 (95% CI 5.7–28.9), p < 0.001) or cone/cone-rod dystrophy (OR = 10.2 (95% CI 3.3–31.8), p < 0.001) was significantly associated with higher odds of having foveal hypoplasia when compared to the control group. Having macular dystrophy on the other hand was not significantly related with higher odds of having hypoplasia when compared to controls (OR = 1.6 [95% CI 0.3–7.9], p = 0.58). Males had significantly and independently higher odds of having foveal hypoplasia regardless of phenotype (OR = 2.4 (95% CI 1.3–4.6), p = 0.006). Age was not significantly associated with foveal hypoplasia (OR = 1.1 (95% CI 0.9–1.3), p = 0.29) (Table 4).
In our univariate analysis, the RPGR group (n = 15) and its matched control group (n = 15) both had 5/15 (33.3%) females. The RPGR group had a mean (standard deviation) age of 34.0 (15.1) while the matched control’s values were 34.7 (13.0). The prevalence of foveal hypoplasia in the RPGR group was 8/15 (53.3%), which was significantly higher than the matched controls (0/15, 0.0%) (p = 0.002). None of our three other genotype groups, ABCA4 (1/22, 4.5% vs. 1/22, 4.5%, p = 1.00), USH2A (4/24, 16.7% vs. 2/24, 8.3%, p = 0.67), and PRPH2 (2/10, 20.0% vs. 1/10, 10.0%, p = 1.00), had a prevalence of foveal hypoplasia that was statistically significantly higher than their matched controls (Table 5).
To investigate the impact of foveal hypoplasia on visual acuity, we analyzed the rod-cone dystrophy group, as it was the largest in our cohort. The rod-cone dystrophy phenotype was divided into three groups based on foveal anatomy: normal (n = 78), grade one (n = 33), and atypical foveal hypoplasia (n = 10). Better eye visual acuity had a mean ±SD of 0.21 ± 0.28 while worse eye was 0.31 ± 0.36. The result of Welch’s ANOVA comparing the three groups of normal fovea, foveal hypoplasia grade one, and atypical foveal hypoplasia was significant (p = 0.028). Atypical foveal hypoplasia had the highest LogMAR of 0.50 (±0.37), which was significantly higher than grade one 0.16 (±0.17) (p = 0.038). Grade one LogMAR was not significantly different from normal fovea 0.20 (±0.28) (p = 0.572), and normal fovea was not significantly lower than atypical foveal hypoplasia (p = 0.070). Similar results are reported for worse eye LogMAR, as normal fovea (0.30 ± 0.37), grade one (0.24 ± 0.29), and atypical foveal hypoplasia (0.64 ± 0.36) were significantly different, as measured via Welch’s ANOVA (p = 0.015). Atypical foveal hypoplasia was higher than both normal (p = 0.037) and grade one (p = 0.017), while grade one and normal fovea were not statistically significantly different from each other (p = 0.682) (Figure 1).
4. Discussion
This study reports the prevalence of foveal hypoplasia among controls and patients with genetically confirmed IRDs. Foveal hypoplasia was found to be associated with rod-cone and cone/cone-rod dystrophy. The prevalence of foveal hypoplasia in macular dystrophy was not significantly different from controls. The prevalence of foveal hypoplasia was found to be significantly higher in males regardless of phenotype. Among different genetic diagnoses, the prevalence of foveal hypoplasia was found to be highest in RPGR-associated retinal degeneration.
We report primarily atypical grade foveal hypoplasia in cone/cone-rod dystrophy due to foveal atrophy in these patients. Kuht et al. had a cohort of 310 patients with achromatopsia, and 209 (67.4%) were reported to have atypical foveal hypoplasia that was associated with the genes CNGB3, CNGA3, GNAT2, PDE6C, PDE6H, and ATF6 [4]. Brunetti-Pierri et al. report a prevalence of 14.3% (3/21) in their cohort of CNGA3, CNGB3, and GNAT2 achromatopsia [2]. Thomas et al. also report a high prevalence in their cohort of 8 patients with achromatopsia (CNGB3, CNGA3, and GNAT2), as most of them (7/8, 87.5%) had atypical foveal hypoplasia [3]. We report a high prevalence of foveal hypoplasia in rod-cone dystrophy that is mainly grade one. Rodriguez-Martinez et al. reported on a cohort of 15 patients with Leber congenital amaurosis and 2 patients with retinitis pigmentosa (RP) who were all CRB1-mutation positive, in which 12/15 (80.0%) and 2/2 (100%) had foveal hypoplasia, respectively, which was mainly grade one [5]. We report a significantly higher prevalence of foveal hypoplasia in RPGR-associated retinal degeneration compared to other genetic etiologies in our cohort. Even though ABCA4, USH2A, and PRPH2 did not have a foveal hypoplasia prevalence that was significantly higher than controls, we acknowledge the small sample size as a limitation in this result.
We report a higher prevalence of foveal hypoplasia in males regardless of patient group (IRD or control). Beldick et al. reported similar findings, as it was observed that males had a higher prevalence of foveal hypoplasia in a cohort of non-IRD patients [10]. Similarly, Jin et al. eluded that regardless of birth history, males have a thicker foveal structure than females [11]. In our study, we found that RPGR-disease-causing variants were associated with foveal hypoplasia. This could partly explain why foveal hypoplasia may be more prevalent in males as RPGR variants cause X-linked RP, which is much less prevalent in females.
Our control group had a low prevalence of foveal hypoplasia. Similar results have been reported by Noval et al., whereby they examined 286 normal patients and found that 1.7% (5 patients) of their cohort had foveal hypoplasia [12].
It has been well documented that RPE melanin pigment is important for foveal development. Ocular and oculocutaneous albinism, in which there is a lack of RPE melanin, have a higher prevalence and greater severity of foveal hypoplasia compared to other IRDs, and even albinism carriers can have abnormal foveal morphology [1,13,14,15]. The genetic etiologies in this study are not known to play a role in RPE pigmentation, and the mechanism of foveal hypoplasia in these patients is not known.
We report that there is no significant difference in central best corrected vision between foveal hypoplasia grade one and normal foveae, suggesting that complete formation of the foveal pit is not necessarily a requirement of full foveal visual functionality, which is consistent with prior reports by Marmor et al. [7]. Similarly, previous reports have shown that a fully formed foveal pit is not necessary for foveal cone packing or a foveal avascular zone [16,17]. Foveal hypoplasia with photoreceptor degeneration showed a decrease in worse eye vision when compared to normal foveae, which is not surprising and is consistent with previous studies [1,4]. In comparing better eye visual acuity, normal foveae were not statistically significantly different than foveae with atypical hypoplasia, likely due to a small sample size.
This study has several limitations. As a retrospective chart review, the OCT protocol was standard of care and was not ideally designed for this study. However, the OCT protocol was standardized and was applied equally to the IRD and control groups, and showed a significant difference in foveal hypoplasia prevalence between the two groups. Any limitations of the protocol would be systematic and would apply to both groups and therefore should not bias the results. Second, we excluded any patients with poor OCT image quality. This could result in exclusion of patients with foveal hypoplasia and poor fixation and/or nystagmus leading to reduced OCT quality. Third, OCT images were classified by a single grader, which could bias the results. Multiple graders with inter-rater reliability (precision) estimations would increase the validity of results. Even though a single grader evaluated the OCT images, they were blinded to the IRD phenotype, and the prevalence rates achieved in this study are comparable with what was previously reported in the literature. Fourth, since these are rare diseases, many of the comparisons were underpowered to detect a difference between groups. However, the multiple logistic regression comparing the three phenotypes to the control group (Table 4), the prevalence of foveal hypoplasia in patients with RPGR variants (Table 5), and the comparisons of visual acuity (Figure 1) were powered with >80% probability of detecting a difference. Lastly, the study population was not evenly distributed among IRD phenotypes, but the proportions we present are reflective of the general phenotype prevalence [8].
5. Conclusions
Our study evaluated several genetically diagnosed IRDs. Whereas the link between specific gene mutations and foveal development remains to be studied, we confirm that IRDs involving physiologically distinct forms of vision (rod-cone and cone/cone-rod) are associated with foveal hypoplasia. Based on our findings, the detection of foveal hypoplasia in a patient with reduced vision should prompt consideration of an inherited retinal disease.
Author Contributions
Conceptualization, A.T.F.; methodology, A.T.F., R.A. and K.T.J.; software, R.A.; validation, R.A. and A.T.F.; formal analysis, R.A.; investigation, R.A. and A.T.F.; resources, A.T.F., K.T.J., K.B. and D.S.; data curation, R.A., K.B. and D.S.; writing—original draft preparation, R.A. and A.T.F.; writing—review and editing, R.A., A.T.F. and K.T.J.; visualization, R.A.; supervision, A.T.F.; project administration, A.T.F.; funding acquisition, A.T.F. and K.T.J. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of the University of Michigan’s Kellogg Eye Center (protocol code is HUM00028413, date of initial approval 8 April 2009).
Informed Consent Statement
Patient consent was waived due to the fact that this study goes under the category of secondary analysis of pre-existing datasets. Furthermore, the research involves no more than minimal risk to the subjects, it could not practicably (i.e., feasibly) be carried out without the waiver or alteration, and the waiver or alteration will not adversely affect the rights and welfare of the subjects.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author (A.T.F.) upon reasonable request for protecting data privacy.
Acknowledgments
A.T.F. acknowledges support from 1R01EY036422 and an unrestricted grant from Research to Prevent Blindness, and K.T.J. acknowledges support from 1R01EY035016-01.
Conflicts of Interest
The authors declare no conflicts of interest.
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Figure 1.
Comparison of better and worse eye LogMAR visual acuity based on foveal anatomy, p values in bold and italic are significant (p < 0.05). Mean values were compared through Welch’s AOVA followed by Games–Howell post-hoc testing. The groups compared were normal (n = 78), grade one (n = 33), and atypical foveal hypoplasia (n = 10). Mean (*), median (transverse bold line), 25th percentile (lower border of blue box), 75th percentile (upper border of blue box), and range without outliers (upper and lower whiskers outside of the blue box) are presented.
Figure 1.
Comparison of better and worse eye LogMAR visual acuity based on foveal anatomy, p values in bold and italic are significant (p < 0.05). Mean values were compared through Welch’s AOVA followed by Games–Howell post-hoc testing. The groups compared were normal (n = 78), grade one (n = 33), and atypical foveal hypoplasia (n = 10). Mean (*), median (transverse bold line), 25th percentile (lower border of blue box), 75th percentile (upper border of blue box), and range without outliers (upper and lower whiskers outside of the blue box) are presented.
Table 1.
Patient demographics.
| Overall | Control | IRD | p Value | |
|---|---|---|---|---|
| Sample (n) | 357 | 182 | 175 | - |
| Age, mean (SD) | 45 (16.6) | 52 (13.8) | 38 (17.1) | <0.001 1 |
| Female, n (%) | 180 (50.4%) | 95 (52.2%) | 85 (48.6%) | 0.49 2 |
| Race and ethnicity, n (%) 3 | ||||
| White | 278 (77.9%) | 137 (75.3%) | 141 (80.6%) | 0.31 2 |
| Black or African American | 33 (9.2%) | 21 (11.5%) | 12 (6.9%) | |
| Asian | 25 (7.0%) | 14 (7.7%) | 11 (6.3%) | |
| Multiple | 4 (1.1%) | 3 (1.6%) | 1 (0.6%) | |
| Unknown race | 17 (4.8%) | 7 (3.8%) | 10 (5.7%) | |
| Non-Hispanic | 319 (89.4%) | 166 (91.2%) | 153 (87.4%) | 0.07 2 |
| Hispanic | 16 (4.5%) | 12 (6.6%) | 4 (2.3%) | |
| Unknown ethnicity | 22 (6.2%) | 4 (2.2%) | 18 (10.3%) | |
| LogMAR Visual acuity, Mean (SD) | ||||
| Better eye | 0.1 (0.2) | 0.0 (0.1) | 0.3 (0.3) | <0.001 1 |
| Worse eye | 0.2 (0.3) | 0.0 (0.1) | 0.4 (0.4) | <0.001 1 |
| Foveal Hypoplasia, n (%) | 62 (17.4%) | 8 (4.4%) | 54 (30.9%) | <0.001 2 |
| Phenotype, n (%) 4 | - | - | - | |
| Rod-cone dystrophy | 123 (70.3%) | |||
| Cone/cone-rod | 22 (12.6%) | |||
| Macular dystrophy | 30 (17.1%) | |||
| Genetic diagnosis, n (%) 4 | - | - | - | |
| USH2A | 30 (17.1%) | |||
| ABCA4 | 25 (14.3%) | |||
| RPGR | 18 (10.3%) | |||
| PRPH2 | 10 (5.7%) |
IRD = Inherited retinal diseases; SD = standard deviation; LogMAR = logarithm of the minimum angle of resolution; USH2A = usherin; ABCA4 = ATP binding cassette subfamily A member 4; RPGR = retinitis pigmentosa GTPase regulator; PRPH2 = peripherin-2. 1 Estimated using Welch’s t-test; 2 estimated using chi-square test of independence; 3 cases with unknown data (unknown race, unknown ethnicity) were excluded from the analysis comparing cases with controls; 4 sample size = 175, includes only patients with inherited retinal disease having undergone genetic testing, control group is excluded.
Table 2.
Foveal anatomy and visual acuity per phenotype.
| Total Sample (n = 357) | ||||
| Rod-cone dystrophy (n = 123) | Cone/cone-rod dystrophy (n = 22) | Macular dystrophy (n = 30) | Control group (n = 182) | |
| LogMAR visual acuity, median (IQR) | ||||
| Better eye | 0.1 (0.0–0.3) | 0.5 (0.2–0.7) | 0.3 (0.1–0.5) | 0.0 (0.0–0.0) |
| Worse eye | 0.2 (0.1–0.4) | 0.7 (0.3–1.0) | 0.5 (0.3–0.7) | 0.0 (0.0–0.0) |
| Foveal anatomy, n (%) [95% CI] | ||||
| Normal | 79 (64.2%) [55.7–72.7%] | 14 (63.6%) [43.5–83.7%] | 28 (93.3%) [84.4–102.2%] | 174 (95.6%) [92.6–98.6%] |
| Foveal hypoplasia | 44 (35.8%) [27.3–44.3%] | 8 (36.4%) [16.3–56.5%] | 2 (6.7%) [−2.2–15.6%] | 8 (4.4%) [1.4–7.4%] |
| Foveal hypoplasia (n = 62) | ||||
| Rod-cone dystrophy (n = 44) | Cone/cone-rod dystrophy (n = 8) | Macular dystrophy (n = 2) | Control group (n = 8) | |
| Grade one, n (%) [95% CI] | 34 (77.3%) [64.9–89.7%] | 1 (12.5%) [−10.4–35.4%] | 0 (0.0%) [0–0%] | 8 (100.0%) [100–100%] |
| Atypical | 10 (22.7%) [10.3–35.1%] | 7 (87.5%) [64.6–110.4%] | 2 (100.0%) [100–100%] | 0 (0.0%) [0–0%] |
IQR = interquartile range; LogMAR = logarithm of the minimum angle of resolution.
Table 3.
Foveal anatomy and visual acuity per genotype.
| USH2A (n = 30) | ABCA4 (n = 25) | RPGR (n = 18) | PRPH2 (n = 10) | |
|---|---|---|---|---|
| Foveal anatomy, n (%) [95% CI] | ||||
| Normal | 23 (76.7%) [61.6–91.8%] | 23 (92.0%) [81.4–102.6%] | 9 (50.0%) [26.9–73.1%] | 8 (80.0%) [55.2–104.8%] |
| Foveal hypoplasia | 7 (23.3%) [8.2–38.4%] | 2 (8.0%) [−2.6–18.6%] | 9 (50.0%) [26.9–73.1%] | 2 (20.0%) [−4.8–44.8%] |
| LogMAR visual acuity, median (IQR) | ||||
| Better eye | 0.1 (0.0–0.2) | 0.3 (0.1–0.5) | 0.1 (0.1–0.2) | 0.1 (0.0–0.5) |
| Worse eye | 0.1 (0.1–0.3) | 0.5 (0.3–0.8) | 0.2 (0.2–0.6) | 0.3 (0.2–0.6) |
USH2A = usherin; ABCA4 = ATP binding cassette subfamily A member 4; RPGR = retinitis pigmentosa GTPase regulator; PRPH2 = peripherin-2; IQR = interquartile range; LogMAR = logarithm of the minimum angle of resolution.
Table 4.
Multivariable logistic regression for presence of foveal hypoplasia regardless of grade.
| Variable | Reference | OR (95% CI) | p Value |
|---|---|---|---|
| Patient subgroup | |||
| Rod-cone dystrophy | Control group | 12.9 (5.7–28.9) | <0.001 |
| Cone/Cone-rod dystrophy | Control group | 10.2 (3.3–31.8) | <0.001 |
| Macular dystrophy | Control group | 1.6 (0.3–7.9) | 0.58 |
| Gender | |||
| Male | Female | 2.4 (1.3–4.6) | 0.006 |
| Age (per 10 y increment) | - | 1.1 (0.9–1.3) | 0.29 |
Table 5.
Prevalence of foveal hypoplasia by genotype.
| ABCA4-control match 1 | |||
| ABCA4 (n = 22) | Control group (n = 22) | p = 1.00 2 | |
| Foveal hypoplasia, n (%) [95% CI] | 1 (4.5%) [−4.2–13.2%] | 1 (4.5%) [-4.2–13.2%] | |
| Normal anatomy | 21 (95.5%) [86.8–104.2%] | 21 (95.5%) [86.8–104.2%] | |
| RPGR-control match 3 | |||
| RPGR (n = 15) | Control group (n = 15) | p = 0.002 2 | |
| Foveal hypoplasia | 8 (53.3%) [28.1–78.5%] | 0 (0%) [0–0%] | |
| Normal anatomy | 7 (46.7%) [21.5–71.9%] | 15 (100%) [100–100%] | |
| USH2A-control match 4 | |||
| USH2A (n = 24) | Control group (n = 24) | p = 0.67 2 | |
| Foveal hypoplasia | 4 (16.7%) [1.8–31.6%] | 2 (8.3%) [−2.7–19.3%] | |
| Normal anatomy | 20 (83.3%) [68.4–98.2%] | 22 (91.7%) [80.7–102.7%] | |
| PRPH2-control match 5 | |||
| PRPH2 (n = 10) | Control group (n = 10) | p = 1.00 2 | |
| Foveal hypoplasia | 2 (20.0%) [−4.8–44.8%] | 1 (10.0%) [−8.6–28.6%] | |
| Normal anatomy | 8 (80.0%) [55.2–104.8%] | 9 (90.0%) [71.4–108.6%] | |
ABCA4 = ATP binding cassette subfamily A member 4; RPGR = retinitis pigmentosa GTPase regulator; USH2A = usherin; PRPH2 = peripherin-2. 1 ABCA4 and matched controls had 13/22 (59.1%) females, mean ages (standard deviation) were 37.2 (17.6) and 38.4 (16.7), respectively. 2 p value obtained via Fisher’s exact test. 3 RPGR3 and matched controls had 5/15 (33.3%) females, mean ages (standard deviation) were 34.0 (15.1) and 34.7 (13.0), respectively. 4 USH2A and matched controls had 12/24 (50.0%) females, mean ages (standard deviation) were 43.9 (15.3) and 44.4 (14.7), respectively. 5 PRPH2 and matched controls had 4/10 (40%) females, mean ages (standard deviation) were 60.6 (7.8) and 59.6 (8.2), respectively.
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MDPI and ACS Style
Abuzaitoun, R.; Branham, K.; Schlegel, D.; Jayasundera, K.T.; Fahim, A.T. The Prevalence of Foveal Hypoplasia in Inherited Retinal Diseases. J. Clin. Transl. Ophthalmol. 2025, 3, 11. https://doi.org/10.3390/jcto3030011
AMA Style
Abuzaitoun R, Branham K, Schlegel D, Jayasundera KT, Fahim AT. The Prevalence of Foveal Hypoplasia in Inherited Retinal Diseases. Journal of Clinical & Translational Ophthalmology. 2025; 3(3):11. https://doi.org/10.3390/jcto3030011
Chicago/Turabian StyleAbuzaitoun, Rebhi, Kari Branham, Dana Schlegel, K. Thiran Jayasundera, and Abigail T. Fahim. 2025. "The Prevalence of Foveal Hypoplasia in Inherited Retinal Diseases" Journal of Clinical & Translational Ophthalmology 3, no. 3: 11. https://doi.org/10.3390/jcto3030011
APA StyleAbuzaitoun, R., Branham, K., Schlegel, D., Jayasundera, K. T., & Fahim, A. T. (2025). The Prevalence of Foveal Hypoplasia in Inherited Retinal Diseases. Journal of Clinical & Translational Ophthalmology, 3(3), 11. https://doi.org/10.3390/jcto3030011
