Down syndrome is a chromosomal abnormality of the aneuploidy type within the trisomy group characterized by an excess of genetic material on chromosome 21. In Latin America, from 1998 to 2005, the overall rate of Down syndrome was 1.88%. Chile (2.47 per 10,000), Argentina (2.01), and Paraguay (1.98) have an above-average overall rate of Down syndrome. Brazil (1.72), Colombia (1.72), Bolivia (1.55), Venezuela (1.49), Ecuador (1.48), and Uruguay (1.32) have an overall rate of Down syndrome below the average [1]. In the Dominican Republic, there are no exact statistical data on the number of live births with Down syndrome. According to the Comprehensive Care Center for Disabilities, it is estimated that around 143 children are born with this condition.

Most cases do not have a hereditary cause and although any couple can have an affected child, advanced maternal age has been identified as a significant risk factor, such that around the age of 35, one in every 350 women will have a child with Down syndrome [2].

The World Health Organization estimates that there are approximately 2.2 billion people with visual impairment worldwide (approximately 30% of the population). Astigmatism (14.9% in children and 40.4% in adults) is the most common refractive error in children and adults worldwide, followed by hyperopia (4.6% in children and 30.6% in adults) and myopia (11.7% in children and 26.5% in adults). Visual impairment affects more people in nations with less developed economies. In the Americas, the prevalence of astigmatism, hyperopia, and myopia in children was 27.2%, 14.3%, and 8.4%, respectively. For adults, the prevalence of astigmatism, hyperopia, and myopia was 45.6%, 37.2%, and 16.2%, respectively [3].

Ophthalmological manifestations are highly prevalent among the population with Down syndrome, including manifestations that jeopardize visual development. Refractive errors are common, present in 80% of the population, especially hyperopia, occurring in 36.42%, which can lead to amblyopia in otherwise healthy eyes. 7 Among larger studies, strabismus was reported to affect between 18.1% and 57.0% of individuals with Down syndrome, which, in turn, is the main cause of amblyopia [4].

Patients with Down syndrome are a vulnerable group with a greater predisposition to developing ophthalmological disorders due to the physiological and structural characteristics associated with the condition. According to the Ophthalmological Guide to Down Syndrome (Spain, 2014), it is recommended that they have their first ophthalmological visit at 3 months of age, the next at 2.5 years of age, and then a periodic annual check-up thereafter [5]. All of this is intended to help prevent and monitor these patients so that their eye health is as optimal as possible.

The purpose of this study is to describe the ophthalmological alterations present in pediatric patients with Down syndrome treated in the Genetics Unit of Dr. Robert Reid Cabral Children's Hospital. This is intended to improve early detection, intervention, and management of these visual disorders; this is essential for preventing long-term complications, improving quality of life, and facilitating social and educational inclusion. Furthermore, the information obtained through this study could be essential for the design of more effective ophthalmological care and follow-up protocols in pediatric units, contributing to improved visual health in this vulnerable population.

A retrospective, cross-sectional, descriptive, observational study was conducted to describe ophthalmological alterations in patients with Down syndrome.

The study was conducted in the Clinical Genetics Unit of the Dr. Robert Reid Cabral Pediatric Hospital, located at Av. Independencia #2 esq. Abraham Lincoln, Santo Domingo, Dominican Republic.

Inclusion Criteria

• Patient with a clinical and/or cytogenetic diagnosis of Down syndrome and ophthalmological alterations.
• Age 0-16 years.

Exclusion Criteria

• Unavailable medical records.
• Incomplete and/or illegible medical records.

Population and Sample

The population consisted of 309 cases, corresponding to all pediatric patients diagnosed with Down syndrome who attended the outpatient clinic of the Genetics Unit of the Dr. Robert Reid Cabral Children's Hospital. A sample of 265 cases was drawn from this sample, corresponding to the total number of patients with this diagnosis who also presented with an ophthalmological disorder.

Data Collection Method, Technique, and Procedure

The method used to capture the research information was a structured form with eight closed questions containing the research variables: age, sex, clinical manifestations, type of ophthalmological disorder diagnosed, maternal age at the time of pregnancy, age at the time of diagnosis of the ophthalmological disorder, diagnostic findings, imaging studies, and prescribed treatment. These variables were measured using indicators based on these variables, presented as options in each question.

The information for this research was obtained from the clinical records of pediatric patients enrolled in the Genetics Unit at Dr. Robert Reid Cabral Children's Hospital, in addition to an extensive literature review that included scientific articles and journals, websites, and textbooks.

The information obtained was tabulated, computerized, and illustrated in tables/graphs for better interpretation and analysis, using appropriate statistical measures, such as percentages. A database was created in Microsoft Excel.

This study was conducted in compliance with international ethical standards, including the guidelines of the Declaration of Helsinki and the Council for International Organizations of Medical Sciences (CIOMS), as well as the Research Committee of the Dr. Robert Reid Cabral Children's Hospital.

Table 1: Age at diagnosis of ophthalmologic disorders in patients with Down syndrome who have ophthalmologic disorders, Dr. Robert Reid Cabral Children's Hospital. January 2019–December 2024.

Source: Clinical records from the Clinical Genetics Unit, Dr. Robert Reid Cabral Pediatric Hospital.

The age at diagnosis showed a high incidence in the identification of ophthalmological alterations at a very early age, with these being diagnosed in the first two years of life in 91% of the cases studied, followed by a homogeneity in the other age ranges: 5% were diagnosed between 3 and 5 years, 2% between 6 and 8 years, and 2% between 9 and 13 years of age. Early diagnosis allows for early intervention in certain alterations that can put the visual and cognitive development of individuals at risk, such as refractive errors.

Table 2: Maternal age at the time of gestation in patients with Down syndrome who have ophthalmological alterations, Dr. Robert Reid Cabral Pediatric Hospital. January 2019–December 2024.

Source: Clinical records from the Genetics Unit, Dr. Robert Reid Cabral Pediatric Hospital.

The highest incidence was found in women aged 36 to 40, at 27%; this coincides with previously conducted studies establishing an increased likelihood of having children with Down syndrome after age 35.2 In second place in terms of frequency were women who conceived between the ages of 18 and 25, at 22%, followed by women who conceived between the ages of 31 and 35, at 18%, and women who conceived between the ages of 26 and 30, at 17%. The age ranges with the lowest incidence were the extremes, with women over 41, at 13%, and those under 18, at 3%. The distribution of maternal age in the observed cases reflects a combination of the individual risk associated with age and the prevalence of pregnancies in each age group. The peak in the 36-40 age group highlights the importance of advanced maternal age as a significant risk factor. This is extremely useful when conducting genetic counseling for reproductive purposes in women in this age range. It can be used to develop awareness campaigns aimed at providing guidance on the risks associated with pregnancy over the age of 35 and its association with chromosomal abnormalities such as Down syndrome.

Table 3: Sex of Down syndrome patients with ophthalmologic disorders, Dr. Robert Reid Cabral Children's Hospital. January 2019–December 2024.

Source: Clinical records from the Genetics Unit, Dr. Robert Reid Cabral Pediatric Hospital.

In this study, the most affected sex was male, representing 58.9%, this contrasts with the results carried out in Istanbul, Turkey by Adem Ugurlu and Emre Altinkurt, in 2020 where the most affected sex was female, with 52.3%.

Table 4: Ophthalmologic Changes in Patients with Down syndrome, Dr. Robert Reid Cabral Pediatric Hospital. January 2019–December 2024.

Source: Clinical records from the Genetics Unit, Dr. Robert Reid Cabral Pediatric Hospital.

The most common ophthalmological alteration was found to be oblique palpebral fissure, accounting for 76.6% of cases, followed by epicanthal fissure (58.9%), and then hypertelorism (49.1%). The other alterations were significantly less common. These results are consistent with those reported by Muñoz Ortiz et al. in Bogotá, Colombia, in 2022, where oblique fissures, epicanthal fissures, and epiblepharon had a prevalence greater than 70% [1]. The three most common ophthalmological changes were anatomical. These changes are more common due to the ease of diagnosis compared to physiological changes and/or due to patients' lack of adherence to follow-up appointments, as well as failure to follow physician guidelines. Ophthalmological changes are underdiagnosed.

Table 5: Clinical manifestations of ophthalmologic disorders in patients with Down syndrome, Dr. Robert Reid Cabral Pediatric Hospital. January 2019–December 2024.

Source: Clinical records from the Genetics Unit, Dr. Robert Reid Cabral Pediatric Hospital.

Unlike other previous studies, where the most common refractive error was hyperopia, in this investigation the most common was myopia, accounting for 2.3%. Furthermore, certain disorders investigated in this study, such as cataracts, glaucoma, keratoconus, papilledema, and hyperopia, were found to be zero or almost zero in some cases, possibly due to a lack of diagnosis rather than a low actual prevalence. In addition to the ophthalmological disorders already mentioned, other less frequent disorders were found in the results: pseudostrabismus, synophris, tear duct stenosis, bilateral eyelid ptosis, exophthalmos, microphthalmia, and fistula in the ocular region of the eye crease, excessive tearing, and ametropia. Regarding the clinical manifestations, these were mostly consistent with the ophthalmological alterations found, the most prevalent was the upward fissure occupying 75.6%, followed by the separation of the internal edges with 51.6%, a discrepancy between the clinical manifestations and the ophthalmological alterations is the fact that there is only one case of cataracts, there are two patients with leukocoria, this because one of these is of unknown origin.

Table 6: Relationship between cytogenetic diagnosis of Down syndrome by karyotype and frequency of ophthalmological abnormalities present, Dr. Robert Reid Cabral Pediatric Hospital. January 2019–December 2024.

Source: Clinical records from the Genetics Unit, Dr. Robert Reid Cabral Pediatric Hospital.

In patients without a karyotype, oblique palpebral fissure was the main ophthalmological abnormality, present in 160 of them, followed by epicanthus, which was observed in 126 cases, and hypertelorism in 101. These results are consistent with those reported in various literature, where these abnormalities are part of the typical dysmorphic phenotype in patients with Down syndrome [2]. These results are like those obtained during the Munoz Ortiz et al. study in Colombia, which established that the most frequent ocular abnormalities (prevalence > 70%) were oblique fissures, epicanthus, and epiblepharon [1]. Regarding eyeball abnormalities, 36 patients presented strabismus, 11 nystagmus, and 11 myopia. No cases of astigmatism or hyperopia were identified, which could be due to an underestimation of these refractive errors. Telecanthus was evident in only 10 patients. Other less frequent but clinically significant alterations are 1 case of optic nerve hypoplasia, 1 case of cataracts and 2 cases of Brushfield spots that are characteristic of Down syndrome.

It should be noted that the high prevalence of oblique palpebral fissure, epicanthus, and hypertelorism can serve as an early warning sign for healthcare professionals to identify Down syndrome in newborns and infants. This early suspicion can lead to more timely referral to pediatric genetics and ophthalmology specialists. This allows for more timely interventions and follow-up care tailored to the patient's needs, which can improve their quality of life and development.

Regarding patients whose medical records did include karyotypes, the three causative mechanisms of Down syndrome found were free trisomy, Robertsonian translocation, and mosaicism. The most common ophthalmological alteration in all three patient groups is oblique palpebral fissure, especially in free trisomy (36 cases) and only two cases in patients with mosaicism and Robertsonian translocation. This suggests that the characteristic is common and independent of karyotype.

Alterations such as epicanthus were evident in 24 patients with free trisomy; only two cases were recorded in mosaicism and Robertsonian translocation. Hypertelorism was identified in 25 patients with free trisomy, only in three patients with Robertsonian translocation, and no cases of mosaicism. The following alterations were present only in patients with free trisomy: strabismus in eight cases, nystagmus in five, astigmatism in four, myopia in three, telecanthus in three, and Brushfield spots in three patients. On the other hand, no alterations such as cataracts, optic nerve hypoplasia, papilledema, hyperopia, keratoconus, glaucoma, or epiblepharon were identified in any of the patients with karyotyping performed. This may be due to the low actual prevalence or diagnostic limitations.

These results allow us to infer that patients with free-range trisomy present with a greater number and variety of ophthalmological abnormalities, both structural and functional. In contrast, patients with mosaicism present with abnormalities less frequently, with a milder or attenuated phenotype. Knowing these data allows the medical team, when faced with a karyotype with a free-range trisomy result, to be more alert and anticipate the possible appearance of a wider range of ophthalmological problems, implementing more exhaustive follow-up from an early age and urging family members to understand the importance of ophthalmological follow-up in these cases.

Table 7: Diagnostic method used to determine ophthalmologic abnormalities in patients with Down syndrome, Dr. Robert Reid Cabral Pediatric Hospital. January 2019–December 2024.

Source: Clinical records from the Genetics Unit, Dr. Robert Reid Cabral Pediatric Hospital.

Regarding the diagnostic method used in the 265 patients studied, the clinical history was used in 259 patients, representing 98.5% of cases, suggesting that this method remains the fundamental basis for initial evaluation and diagnostic guidance in any medical setting.7 Secondly, the pupillary light reaction test was used in 31.6% of cases (83 patients), and ophthalmoscopy was used in 10.3% of cases (27 patients). Diagnostic methods such as retinoscopy (0.4%) and the Snellen test (1.9%) were used in a small proportion, which is surprising considering their usefulness in assessing visual acuity and refractive errors. Campimetry, Autorefractometry and Tonometry were not used in any of the cases.

Table 8: Treatment used for ophthalmologic disorders diagnosed in patients with Down syndrome, Dr. Robert Reid Cabral Children's Hospital. January 2019–December 2024.

Source: Clinical records from the Genetics Unit, Dr. Robert Reid Cabral Pediatric Hospital.

Among the patients studied, 62.3% presented morphological alterations that, while producing facial dysmorphic features, did not require any treatment, such as oblique palpebral fissures, epicanthus, hypertelorism, among others. The 31.3% who did not receive any specific treatment may be interpreted as a structural limitation (lack of resources, absence of specialists, or a purely diagnostic approach without intervention), or as a sample composed primarily of patients without pathologies requiring immediate treatment.

Vision therapy was administered in 7 cases (2.6%), corrective lenses were used in 12 patients (4.5%), and eye drops were prescribed in only 2 patients (0.8%). Surgical procedures such as phacoemulsification, laser peripheral iridotomy, and penetrating keratoplasty were not administered in any case (0%). This is due to the low prevalence of patients with surgically treatable conditions in the study sample.

The Genetics Unit of Dr. Robert Read Cabral Children's Hospital received 309 patients with Down syndrome between January 2019 and December 2024. Of these, 265 were diagnosed with ophthalmological disorders, representing 85.7%. In the sample studied, the maternal age most frequently occurred in women between 36 and 40 years of age, representing 27%. Most patients who attended the unit were diagnosed with the disorder between 0 and 2 years of age, corresponding to 91%. The most prevalent sex in patients with Down syndrome and ophthalmological disorders was male (59%).

Regarding clinical manifestations, the most frequent are oblique palpebral fissure present in 76.6% of patients, followed by epicanthus in 58.9% and hypertelorism in 49.1%. Regarding the link between ophthalmological alterations and the karyotype presented by the patients, oblique palpebral fissure was the main ophthalmological alteration in patients without a present karyotype in 160 cases, followed by epicanthus, which was observed in 126 cases, and hypertelorism in 101 patients. Regarding patients who did have a karyotype in their clinical records, the 3 causative mechanisms of Down syndrome found were free trisomy, Robertsonian translocation, and mosaicism. The most common ophthalmological abnormality in all three patient groups is oblique palpebral fissure, especially in free trisomy (36 cases) and only two cases in patients with mosaicism and Robertsonian translocation.

The most used diagnostic method in the 265 patients studied was clinical history (98.5%). Regarding treatment, 62.3% of patients presented morphological alterations that, while producing dysmorphic facial features, did not require any intervention.

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