Long-Term Follow-up Results and Visual Outcomes of Childhood Glaucoma in the Black Sea Region of Turkey

doi:10.21203/rs.3.rs-4320896/v1

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Long-Term Follow-up Results and Visual Outcomes of Childhood Glaucoma in the Black Sea Region of Turkey

https://doi.org/10.21203/rs.3.rs-4320896/v1

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published 29 Aug, 2024

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Purpose

To investigate long-term visual outcomes and factors associated with low vision in patients with childhood glaucoma.

Materials and Methods

A retrospective review was conducted on the medical records of pediatric glaucoma patients at the Ondokuz Mayis University Ophthalmology Clinic from 2005 to 2023. The patients were categorized into three groups: primary congenital glaucoma (PCG), secondary childhood glaucoma, and glaucoma following cataract surgery (GFCS). Groups were analyzed regarding visual acuity (VA), ocular conditions and comorbidities, and the cause of visual impairment. The study also investigated the potential risk factors associated with visual impairment.

Results

A total of 105 eyes of 60 patients with a mean age of 9,7 ± 5,5 years were included in the study. The mean VA in logMAR was 0,59 ± 0,52. At the final follow-up, 28,6% had good VA (≥ 20/50), 21,9% had moderate VA (20/60–20/200), and 28,6% had poor VA (< 20/200). The final mean intraocular pressure (IOP) was 16,2 ± 6,2 mmHg. Amblyopia was the leading cause of vision loss (38,2%), followed by glaucomatous damage (36,4%). Patients with GFCS had a higher rate of visual impairment (40,6%) and refractive error. The results of the regression analysis showed that low vision was associated with undergoing more than two surgeries, high IOP at baseline, high initial and final cup-to-disc (C/D) ratio, and high initial central corneal thickness (CCT) (CI: 95%, p = 0,05, p = 0,013, p = 0,003, p = 0,013, respectively).

Conclusion

Good VA can be achieved in 28,6% of childhood glaucoma cases. However, the VA prognosis may be worse in patients with GFCS. Achieving good visual outcomes in childhood glaucoma requires timely and effective treatment, consideration of risk factors, and management of amblyopia and ocular comorbidities.

primary congenital glaucoma

glaucoma following cataract surgery

secondary congenital glaucoma

visual acuity

risk factor

visual prognosis

Childhood glaucoma is a heterogeneous group causing similar outcomes due to structural damage due to elevated intraocular pressure. It is responsible for approximately 5% of blindness in childhood. The visual prognosis is more severe than adult glaucoma. In addition, optic nerve and visual field damage may result in axial elongation, leading to myopia, increased corneal diameter, corneal edema, and ophthalmia, especially below the age of 3 years.¹

The Childhood Glaucoma Research Network (CGRN) defined a classification system for childhood glaucoma.² Accordingly, primary childhood glaucoma includes PCG and juvenile open-angle glaucoma (JOAG). Secondary childhood glaucoma includes subgroups associated with non-acquired ocular anomalies, associated with non-acquired systemic anomalies, and associated with acquired anomalies. Patients who receive a diagnosis of glaucoma only after cataract surgery are considered to have glaucoma following cataract surgery.

In a child with the suspicion of glaucoma, accurate diagnosis, intraocular pressure control, and prevention of amblyopia are of great importance in terms of prognosis, and patient follow-up should be performed for many years to optimize the prognosis.

Visual prognosis of PCG cases has been reported in many studies, and risk factors associated with low vision have been investigated. Visual prognosis differs in different geographic regions, and the proportion of eyes achieving good VA ranges from 26.9–79%.^3–10 Young age at diagnosis, unilateral disease, multiple surgeries, glaucomatous optic atrophy, and corneal opacity have been associated with poor visual prognosis for PCG.^8,10

The first-line management strategy in the treatment of PCG is surgical treatment. JOAG and secondary childhood glaucoma can initially be managed with medical treatment. Although the treatment of congenital glaucoma is aimed at normalizing IOP and preventing further damage to the optic nerve, visual rehabilitation remains integral to clinical management.

Although many studies have evaluated short and/or long-term visual outcomes and risk factors for PCG, few data are available on secondary childhood glaucoma. This study aimed to retrospectively determine the long-term visual prognosis and possible risk factors for vision loss in patients with PCG and secondary childhood glaucoma due to non-acquired anomalies and GFCS in Turkey.

Subjects: Patients diagnosed and treated for glaucoma by the same clinician (NA) in Ondokuz Mayıs University Ophthalmology Clinic between 2005 and 2023 were retrospectively analyzed. All patients with glaucoma who were under 18 years of age at the time of diagnosis were reviewed for diagnosis and classification based on the CGRN guideline (Fig. 1). The classification was as follows: patients with primary congenital glaucoma (group 1), patients with a congenital ocular anomaly or systemic syndrome (group 2), and patients with GFSC (group 3). Also, participants whose VA can be assessed were divided into two groups, good (VA ≥ 20/50) and low vision, to analyse the data from a broad perspective of visual impairment. Patients with JOAG and acquired glaucoma were excluded due to insufficient sample size and insufficient data for statistical analysis.

Patients who were followed for suspicion of glaucoma and did not receive treatment were not included in the study to avoid causing statistically biased results. All included patients received surgical or medical treatment. The surgical treatments were angle surgeries (goniotomy, trabeculotomy) and filtration surgeries (trabeculectomy, drainage implantation surgery).

Patients were excluded from the study if they were 18 years of age or older at the time of diagnosis of trauma glaucoma and had previously treatment at another center. Patients with identifiable retinal pathology (e.g., Behcet's uveitis), active uveitis during the study (e.g., Herpes Simplex Uveitis), corneal abnormalities, associated refractive errors not attributable to childhood glaucoma, and patients with visual pathway pathologies were excluded from the study.

Patients underwent regular examinations every three months or more frequently as required. The study was approved by the Ondokuz Mayıs University Clinical Research Ethics Committee and conducted by the Declaration of Helsinki. Informed consent was waived due to the retrospective nature of the study.

Ocular Examinations and Data Collection:

Personal data included age, sex, age at diagnosis, ocular and systemic comorbidities, mean follow-up, surgeries performed, number of surgeries performed, presence of visual impairment, spectacle, and contact lens wear(in patients with no filtration bleb). Ophthalmic findings included VA, the spherical equivalent of refractive error (SE), IOP, corneal diameter (HCD), corneal thickness (CCT), corneal status, anterior segment abnormalities (e.g., aniridia, Axenfeld-Rieger anomaly), C/D ratio and other glaucomatous disc findings. The recorded VA values were converted to logMAR equivalents. VA, evaluated as finger counting, hand movements, light perception, or absence of light perception, was recorded as logMAR values of 1,4, 2,7, 3,7, and 4,7, respectively. Patients who were uncooperative and could only be evaluated for light object tracking were excluded from the statistical analysis of VA. Cycloplegic refraction was performed for each patient at the first and last examination, and SE was recorded. In cooperative patients, IOP was measured with the Goldmann applanation tonometer. In non-compliant and underage patients, IOP was measured under general anesthesia using the Tono-Pen AVIA device (Reichert Technologies, Depew, NY, USA). Detailed slit lamp examination findings were recorded, including corneal comorbidities C/D ratio. CCT was measured using the UP-1000 ultrasonic pachymeter (Nidek Inc, Freemont, CA, USA). The corneal diameter was measured with a corneal caliper under general anesthesia in discordant and younger patients and under topical anesthesia (0,5% proparacaine) in cooperative patients under office conditions.

The visual field test was not included in the analysis due to the inability of most patients to perform an objective visual field test at the time of enrolment in the study and the lack of sufficient statistical data.

Evaluation of Visual Outcomes:

The best corrected VA were classified as good (20/50 and better), moderate (< 20/50–20/200), and poor (less than 20/200). Vision less than 20/50 was considered low vision. Groups 1, 2, and 3 were analysed for VA levels and recorded variables. Good (VA ≥ 20/50) and low vision (VA < 20/50) groups were compared in terms of variables. Possible risk factors for low vision were identified and recorded as corneal opacification, glaucomatous optic neuropathy, amblyopia, and nystagmus. Glaucomatous damage was considered in patients with focal notching of the disc, retinal nerve fiber defects, progressive growth of cupping, and asymmetric cupping.

Participants whose VA was not age-expected and whose VA was significantly worse than the fellow eye in unilateral disease and eyes without corneal complications or significant glaucomatous disc damage that could explain the visual impairment and eyes with the following refractive errors were considered potentially amblyopia: hyperopia/myopia ≥ 4,00 diopters (D), astigmatism ≥ 2 D, or anisometropia ≥ 1,5 D. In addition, refraction between − 0,75 D and + 0,75 D was considered as emmetropia, -1,00 D and − 6,00 D as mild-moderate myopia, above − 6,00 D as high myopia, and above + 1,00 D as hyperopia. Patients with VA less than 20/50 at the last examination and who did not have other ocular comorbidities such as optic nerve damage, corneal opacity, and nystagmus were considered amblyopia.

Statistical Analysis:

Statistical analyses were performed with SPSS software (IBM Corp. 2019. IBM SPSS Statistics for Windows, version 26.0. Armonk, NY: IBM Corp). Group differences were analyzed with the Kruskal-Wallis, Chi-square, one-way ANOVA, T-test, and Mann-Whitney U tests. Good and poor vision scores were compared with T-test, Chi-square and Mann-Whitney U-test. Potential risk factors for low vision were evaluated by logistic regression analysis, and a possible risk model was constructed. A p-value of < 0,05 was considered statistically significant.

A total of 105 eyes of 60 patients were included in the study. At the time of participation in the study, the mean age of the cases was 9,7±5,5 years (1-28), the mean age at diagnosis was 15,9±5,8 months, and the mean follow-up time was 83.7±49.1 months. Of the participants, 24 were females and 36 were males. 15 patients had glaucoma in one eye, and 45 had glaucoma in both eyes. Of all cases, 47 (44,8%) were diagnosed with PCG, 23 (21,9%) with secondary childhood glaucoma, and 35 (33,3%) with GFCS. Demographic and clinical data are summarized in Table 1.

Group 1 had the highest number of glaucoma surgeries per eye. (1,1±0,8, p=0,001) Compared to other groups, the rate of female participants was higher in Group 2 (64%, p=0,043). The initial C/D ratio was highest in Group 1 and lowest in Group 3 (0,54±0,24 vs 0,26±0,19, p=0,001). The C/D ratio increased in all groups, and the final C/D ratio was highest in Group 2 (initial C/D: 0,43±0,37 vs final C/D: 0,69±0,38, p=0,024). Mean IOP was 27,4±6,6 mmHg at the initial follow-up and 16,2±6,2 mmHg at the final follow-up, and there was no significant difference between the groups (p=0,794, p=0,663, respectively).

At both the initial and final examination, Group 1 had a significantly larger HCD (p=0,001, p=0,001, respectively). At baseline, the groups had similar CCT (p=0,194). However, at the last follow-up, significant differences in CCT were observed between the groups (p=0,011). CCT regressed in groups 1 and 2 but progressed in group 3.

Mean VA was similar in groups 1 and 2 (p=0,651) but was poorer in group 3. The initial mean SE was 4,06±4,65, and the final mean SE was 0,86±1,88. The SE was significantly hyperopic in the GFCS group (10,49±4,27, p=0,001). It was observed that the initial hyperopia values of all groups decreased and shifted towards myopia. In Groups 1 and 2, patients with myopia and high myopia, respectively, constituted the majority, with values of 36,4% and 55%. In the GFCS group, the majority of patients were hyperopic, accounting for 71% of cases (p=0,002).

Clear corneas constituted the majority in all groups (%63,8). In group 3, 40% of the participants had corneal complications, proportionally different from the other two groups (p=0,011).

The most common cause of low vision was amblyopia (38,2%), followed by glaucomatous optic nerve damage (36,4%). The groups showed similar characteristics regarding the causes of low vision (p=0,510). In Group 3, amblyopia constituted the majority of visual impairment, with a rate of 41,7%. The clinical data and statistical comparisons of primary congenital glaucoma, secondary childhood glaucoma, and GFCS groups are summarized in Table 2.

Initial IOP, number of surgeries per eye, initial and final C/D ratio, initial and final CCT values were significantly higher in participants with low vision (VA <20/50) compared to those with good vision (VA ≥20/50) (p=0,001, p=0,026, p=0,008, p=0,002, p=0,001, p=0,024, p=0,001, respectively). Furthermore, corneal complications were relatively higher for the low vision group (53,7% vs. 24,3%). Both groups had a similar distribution of demographic characteristics. There were no significant differences between the groups in the type of surgery performed, initial and final SE, type of refractive correction, initial and final HCD. Table 3 summarises the clinical characteristics and statistical comparisons of participants with good and low vision.

Logistic regression analysis showed that high initial IOP, high initial CCT, high initial and final C/D ratio, and more than 2 operations were significantly associated with poor VA. Table 4 summarises the logistic regression analysis for low VA.

Our study aimed to determine the visual prognosis in cases with childhood glaucoma and investigate possible risk factors for low vision. In addition, we tried to assess the effect of etiology on visual prognosis and its relation with ocular comorbidities in childhood glaucoma cases. After a mean follow-up of 84,2 months, 28,6% of participants had a VA of 20/50 or better. Good final VA was achieved in 47.2% of PCG cases compared to 33.3% in the secondary childhood glaucoma group and 25% in the GFCS group. This difference may be attributed to the older age at diagnosis, higher final IOP, and shorter follow-up period in the secondary childhood glaucoma group. The secondary childhood glaucoma group underwent less glaucoma surgery than the PCG group, which may highlight the importance of filtration surgery and strict IOP control. The GFCS group had the lowest final IOP. Still, the higher rate of corneal comorbidities, high refractive errors, aphakia, and late age at diagnosis may explain the lack of good final VA.

Different visual results have been reported in many studies of PCG patients. Mandal et al.¹¹ found that 20/60 VA was achieved in 7 of 19 PCG patients (26,9%) with HCD ≥ 14 mm. Yassin SA⁸ reported a VA of 20/50 or better in 27 of 53 eyes (51%) that underwent successful surgical treatment. Fang et al.⁴ reported that a VA of 20/50 and above was achieved in 56% of 95 eyes under IOP control. Our study found that 47,2% of the eyes had a VA of 20/50 or better in PCG. Few studies have linked secondary childhood glaucomas and GFSC with VA. The differences between VA levels can be explained by the fact that our study was conducted on a heterogeneous group with different demographic characteristics, number of operations, and inclusion criteria. Lopes et al. reported that patients in these two groups had worse visual outcomes compared to PCG, which is consistent with our findings.¹²

Lee et al.⁵ suggested that multiple surgeries would have a negative impact on visual prognosis. In our study, the number of glaucoma surgeries per eye was 0,61 ± 0,55 in cases with VA ≥ 20/50 and 1,0 ± 0,84 in cases with VA < 20/50 (p = 0,026). Multiple surgeries are a harbinger of uncontrolled IOP and, therefore, progression of glaucomatous disc damage. It can lead to ocular comorbidities such as corneal opacity, nystagmus, strabismus, and cataracts. Multiple surgeries are also associated with a certain postoperative recovery time, which can cause amblyopia. In parallel, logistic regression analysis showed that multiple surgeries were a risk factor for low vision.

Our study observed an increase in HCD for all groups at the end of the follow-up period, consistent with previous findings for cases with PCG.¹³ The increase in HCD can be attributed to the elevated IOP and the high plasticity of the cornea and sclera in children. Kun et al.¹⁴ suggested horizontal corneal diameter (HCD) is lower in eyes with congenital cataracts. Similarly, in our study, HCD was lower in patients with glaucoma after cataract surgery at the initial and final examination. Factors such as age at glaucoma diagnosis, differences in glaucoma etiology, and IOP control may explain this difference (GFCS participants had lower IOP at the initial and final follow-up). Fang et al.⁴ suggested that preoperative HCD is related to low vision. However, we could not establish a relationship between HCD and low vision.

In cases of PCG without corneal edema, it has been suggested that the CCT is reduced due to the stretching of the tissues. ¹⁵ The CCT decreased at the final examination in both the PCG and secondary childhood glaucoma groups compared to the initial examination. The initial high IOP likely caused corneal edema and increased CCT. However, it has been reported that individuals with congenital cataracts may have a high CCT.^14,16 Similarly, in our study, the CCT increased at the last visit in the group with GFCS compared to the initial visit. Furthermore, it was found that the group with VA < 20/50 had significantly higher CCT both at the initial and the final visit. Regression analysis revealed that higher CCT was associated with a poorer visual outcome. Therefore, it can be concluded that CCT is a visual prognosis marker.

Many studies suggest that myopia is the most common refractive error in PCG patients.^4,8,17 Increased IOP is thought to cause axial elongation of the eye.¹⁷ In our study, we found that myopia was the most common refractive error in PCG and secondary childhood cases (36,4% and 55%, respectively). However, GFCS cases shifted the overall refractive error to hyperopia. The groups differed significantly in terms of refractive error correction. This may be due to the inability to use contact lenses in patients with filtration blebs, the presence of emmetropic patients in the PCG and secondary childhood group, and the high refractive errors in the GFCS group. There was no significant effect of the type of refractive correction in the good and poor vision groups.

Amblyopia is a significant cause of vision loss in childhood glaucoma patients with controlled IOP. The study found that amblyopia was a significant cause of visual impairment, followed by glaucomatous damage. These findings were consistent with previous literature.^4,8,18 Kargı et al.³ suggested that long-term control of IOP and keeping it below 19 mmHg may help preserve vision in patients with childhood glaucoma. Similar to our study, the authors suggested that amblyopia is the most common cause of low vision, and low vision was significantly higher in cases of aphakic glaucoma. In addition, ocular comorbidities such as corneal opacities, cataract, and nystagmus also cause poor visual outcomes, both directly and by causing amblyopia. This situation highlights the importance of the treatment of amblyopia and ocular comorbidities in childhood glaucoma cases.

A limitation of our study was the large number of patients who were unable to comply with the visual examination. As a result, the VA values of these patients could not be included in the study, which limited the sample size. Additionally, we were unable to examine the effect of the retinal nerve fiber layer on visual prognosis due to the poor measurement cooperation of most of the pediatric patients at the time of the study. Visual field tests were not included in the analysis due to an insufficient number of patients who were compatible with the visual field. Axial length follow-up was not possible in most patients due to examination difficulties and therefore could not be included in the analysis. The inclusion of patients with GFCS and the heterogeneity of the study groups may affect the overall refractive error. Some patients may experience a minimization effect due to high refractive error, which could lead to a poor VA prognosis.

Numerous studies in the literature investigate the visual prognosis of PCG. However, limited studies are reporting visual outcomes in patients with secondary congenital glaucoma and GFCS. Our study aimed to determine the factors associated with visual impairment in childhood glaucoma. Regression analysis revealed that high initial IOP, high CCT, more than two surgeries, and high initial and final C/D ratio were associated with visual impairment. Achieving vision above 20/50 in 28.6% of childhood glaucoma patients with controlled IOP is possible. Early and accurate diagnosis, successful treatment, including IOP control, and prevention of amblyopia are crucial for a positive prognosis. These results may be a potential step towards early diagnosis, timely and effective treatment, and management of amblyopia and ocular comorbidities in order to achieve good visual outcomes in childhood glaucoma.

Conflict of interest:

None of the authors has a conflict of interest with this submission.

Financial support: No funding was provided for this manuscript.

Author Contribution

A.G. and L.N. collected patients data, wrote the main manuscript textA.G. prepared Figure 1A.G. prepared Table 1,2, and 3L.N. prepared Table 4All authors reviewed the manuscript.

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Table 1 to 4 are available in the Supplementary Files section.

No competing interests reported.

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Journal Publication

published 29 Aug, 2024

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Editorial decision: Revision requested
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Reviewers agreed at journal
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You are reading this latest preprint version

Long-Term Follow-up Results and Visual Outcomes of Childhood Glaucoma in the Black Sea Region of Turkey

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Journal Publication

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Abstract

Purpose

Materials and Methods

Results

Conclusion

Figures

Introduction

Materials and Methods

Ocular Examinations and Data Collection:

Evaluation of Visual Outcomes:

Statistical Analysis:

Results

Discussion

Conclusion

Declarations

Conflict of interest:

Author Contribution

References

Tables

Additional Declarations

Status:

Journal Publication

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