Lens
Risk of Retinal Detachment After Pediatric Cataract Surgery Birgitte Haargaard,1,2 Elisabeth W. Andersen,1 Anna Oudin,1 Gry Poulsen,1 Jan Wohlfahrt,1 Morten la Cour,2 and Mads Melbye1 1 2
Department of Epidemiology Research, Statens Serum Institut, Denmark Department of Ophthalmology, Glostrup University Hospital, Copenhagen, Denmark
Correspondence: Birgitte Haargaard, Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen, Denmark; [email protected], [email protected]. Submitted: January 21, 2014 Accepted: March 27, 2014 Citation: Haargaard B, Andersen EW, Oudin A, et al. Risk of retinal detachment after pediatric cataract surgery. Invest Ophthalmol Vis Sci. 2014;55:2947–2951. DOI:10.1167/ iovs.14-13996
PURPOSE. To determine the long-term risk of retinal detachment following pediatric cataract surgery and to identify risk factors for retinal detachment. METHODS. We included all children (aged 0 to 17 years) who during the time period of 1977 to 2005 underwent pediatric cataract surgery in Denmark, excluding cataract cases caused by trauma, or acquired systemic or acquired ocular pathology, and cases with ocular anomalies associated with the development of retinal detachment. Cases of cataract were ascertained from the mandatory Danish National Patient Register, and information on retinal detachment was based on medical chart review. RESULTS. Among 1043 eyes of 656 children undergoing surgery for pediatric cataract, 25 eyes (23 children) developed retinal detachment at a median time of 9.1 years after surgery. The overall 20-year risk of retinal detachment was 7% (95% confidence interval [CI]: 3%–11%) among cataract patients. In otherwise normal children having isolated cataract, the risk was 3% (95% CI: 0%–7%). A significantly higher risk of developing retinal detachment was found in children with mental retardation (23% [95% CI: 9%–35%]) or in cataract cases with other ocular or systemic anomalies (16% [95% CI: 6%–24%]). CONCLUSIONS. The estimated overall risk of retinal detachment 20 years after pediatric cataract surgery was 7%, but only 3% for isolated cataract. Particularly high risks of retinal detachment after cataract surgery were associated with mental retardation and having other ocular or systemic diseases. Keywords: pediatric cataract, retinal detachment, epidemiology
mong adults, it is well-known that the risk of retinal detachment after cataract surgery is higher compared with eyes not undergoing cataract surgery. Thus, studies have reported a 7.5 to 8.7 times higher risk 6 or more years after cataract surgery.1,2 The risk of retinal detachment in adults remains higher even 20 years after cataract surgery.3 Among adults without previous cataract surgery, the overall risk of retinal detachment is estimated to be 0.03% per person year.1 In comparison, the occurrence of retinal detachment among children is very rare. Based on data from the Danish National Patient Register, retinal detachment occurs in approximately 0.001% of all children aged 0 to 17 years (la Cour, unpublished observations, 2008). In children, it is recognized that retinal detachment is a late complication to cataract surgery. The condition has been reported to occur on average 23 to 33 years after the primary surgery,4–6 with around one-third occurring within the first 10 years.4,7 Previous studies on the risk retinal detachment after pediatric cataract surgery have short-term follow-up times (3.5 to 6.8 years) and are based merely on aphakic eyes.8–10 Accordingly, there is a lack of large, long-term studies on the risk of retinal detachment after surgery for pediatric cataract including both pseudophakic and aphakic eyes. It is also unknown if different surgical procedures for pediatric cataract have an influence on the risk of later detachment. Before 1990 in Denmark, the most common cataract surgery was lensec-
A
Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783
tomy without posterior capsulorhexis and anterior vitrectomy. After 1990, many surgeons changed surgical technique and included posterior capsulorhexis and anterior vitrectomy as standard procedures in small children undergoing surgery for pediatric cataract. Based on the long existing Danish national registries, we therefore established a population-based cohort of children who had undergone surgery for pediatric cataract during the period of 1977 to 2005. The aim was to evaluate the long-term risk of retinal detachment following pediatric cataract surgery and to look for risk factors for developing retinal detachment in these patients.
METHODS Study Cohort Since 1977, all discharge diagnoses and surgical procedures of patients admitted to public hospitals have been registered in the Danish National Patient Register (NPR). Since 1995 also outpatients have been registered. Based on the information from the NPR, we established a cohort of all children, who were diagnosed with pediatric cataract during the period of 1977 to 2001 before the age of 18 years. We validated the cataract diagnosis by subsequently contacting all relevant hospitals to retrieve and review the children’s medical records. Additional 2947
Retinal Detachment Risk case information was obtained from consultant private ophthalmologists attended by the children. We obtained the complete medical record, including all follow-up visits and consultation data. In Denmark, surgery for retinal detachment is performed only at public hospitals in both children and adults. Information about possible death and emigration was obtained by linkage with the Danish Civil Registration System.11 For this study, only cataract cases (diagnosed between 1977 and 2001) who underwent cataract surgery during the period of 1977 to 2005 were included in the study cohort. Cataract cases caused by trauma, or considered due to acquired systemic (e.g., diabetes) or acquired ocular pathology (e.g., uveitis), were excluded.12,13 We furthermore excluded cataract cases with ocular conditions considered to be highly associated with the development of detachment in itself or after cataract surgery (persistent fetal vasculature [PFV]; neyes ¼ 43) and retinopathy of prematurity (ROP; neyes ¼ 2). Information on retinal detachment following pediatric cataract surgery was obtained from the medical records. Permission to receive data from the national registries was obtained from the Danish Data Protection Agency (2000-410285). The study was approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg ([KF] 01-253/ 00), and it adhered to the tenets of the Declaration of Helsinki.
Follow-up All analyses were based on eyes as the unit. Time at risk was defined for each eye as the time from cataract surgery until time of diagnosis of retinal detachment, date of last visit to an ophthalmologist, emigration or death, date of relevant trauma (neyes ¼ 1), or posterior vitrectomy (neyes ¼ 3), whichever came first. Accordingly, eyes with retinal detachment prior to cataract surgery were not included in the analyses (neyes ¼ 3). The median follow-up time since cataract surgery was 6.8 years (25th quartile, 2.6 years; 75th quartile, 12.8 years).
Statistical Analyses Rate ratios of retinal detachment following surgery of pediatric cataract according to various characteristics were estimated by a Cox proportional hazards regression model with time since surgery as underlying time scale using the procedure PROC PHREG in advanced analytics software (SAS; SAS Institute, Inc., Cary, NC, USA). Age at surgery was analyzed by including age in the regression model with the following categories (in months): 0 to 5, 6 to 11, 12 to 23, 24 to 47, and ‡48 months. A trend was fitted by allowing a linear effect of age at surgery (in months). The outcome for two eyes from the same person can not necessarily be considered independent. The traditional standard errors were therefore substituted by robust standard errors that allows for such a clustered data structure,14 resulting in slightly wider confidence intervals on estimated rate ratios. The cumulative risk of retinal detachment by years since cataract surgery was estimated by Kaplan-Meier estimates using statistical software (Stata 12; StataCorp LP, College Station, TX, USA).
RESULTS During the time period of 1977 to 2005, a total of 1043 eyes of 656 children had a validated diagnosis of pediatric cataract, underwent cataract surgery, and were without other known risk factors for developing retinal detachment (see Methods section). In total, 25 eyes (23 children) with retinal detachment were observed in the study. Median time between cataract surgery
IOVS j May 2014 j Vol. 55 j No. 5 j 2948 and development of retinal detachment was 9.1 years (25th quartile, 5.2; 75th quartile, 16.9 years). Two children developed bilateral retinal detachments. We found only a slight insignificant (P ¼ 0.73) male predominance: 56% (14/25). In the Table, the rate ratios of developing retinal detachment according to possible risk factors are shown. Retinal detachment was significantly higher in eyes of children with mental retardation (rate ratio [RR] ¼ 9.59 [95% CI: 3.89, 23.61], P < 0.001) and in eyes with other ocular or systemic diseases (clinical manifestation; RR ¼ 8.52 [95% CI: 3.28, 22.15], P < 0.001), but also in children having pars plana lensectomy (RR ¼ 4.66 [95% CI: 1.05, 2.63], P ¼ 0.04). However, after adjusting for mental retardation and clinical manifestation, only mental retardation remained significant (RR ¼ 5.26 [95% CI: 1.24, 22.36], P ¼ 0.03), whereas clinical manifestation (RR ¼ 3.39, [95% CI: 0.81, 14.15], P ¼ 0.09) and pars plana surgery (RR ¼ 2.34 [95% CI: 0.38, 14.43], P ¼ 0.36) became insignificant. All other adjusted rate ratios were below 1.7 and insignificant. Due to the higher correlation between mental retardation and clinical manifestation, we investigated their interaction further. No statistically significant interaction was observed (P ¼ 0.43). However, in children without mental retardation, eyes of children having other ocular or systemic diseases had a significantly higher rate of retinal detachment (RR ¼ 4.39 [1.05–18.33], P ¼ 0.04); and in children whose cataract was associated with other ocular or systemic disease, having mental retardation was associated with a significantly higher rate of retinal detachment (RR ¼ 8.12 [1.23–53.48], P ¼ 0.03). RR in eyes in children having both mental retardation and other ocular or systemic diseases compared with children having neither was 14.12 (4.80–1.4), P < 0.001. Due to these additional results, we emphasize in the following both the association with mental retardation and clinical manifestation. Age at surgery did not appear to be associated with risk of retinal detachment. Among children (304 eyes) who received a primary intraocular lens implantation, no cases developed retinal detachment. We also compared surgeons within the present study who had performed more than 50 pediatric cataract surgeries with those having performed less. There was no difference between the two groups on the risk of retinal detachment (RR ¼ 1.24 [95% CI: 1.05, 20.72] P ¼ 0.71). There was no difference in the risk estimates for retinal detachment after cataract surgery performed before 1990 and after 1990 (RR ¼ 1.16 [95% CI: 0.47, 2.89] P ¼ 0.75), when the majority of eyes had primary surgery with posterior capsulorhexis and anterior vitrectomy performed. Figure (A) shows the cumulative risk of retinal detachment by years since cataract surgery. The overall risk of retinal detachment 20 years after pediatric cataract surgery remained 7% (95% CI: 3%, 11%). Including cases with PFV and ROP, the risk was 7% (95% CI: 4%, 11%). Figure (B) shows the cumulative risk of retinal detachment by years since cataract surgery by clinical manifestation. In patients with other ocular or systemic diseases apart from pediatric cataract, the 20-year risk was 16% (95% CI: 6%, 24%) compared with 3% (95% CI: 0%, 7%) in isolated cataract. Figure (C) shows the cumulative risk of retinal detachment by years since cataract surgery by mental retardation. The 20-year risk was 23% (95% CI: 9%, 35%) in patients with mental retardation compared with 3% (95% CI: 0%, 6%) in patients without mental retardation. In 52% (13/25) of the retinal detachment eyes, surgery was not performed because it was considered pointless due to fibrosis. Eight of these eyes had no light perception, two had light perception, one had Snellen visual acuity (VA) of 0.03, one had 0.1, and in one eye, no VA was available.
IOVS j May 2014 j Vol. 55 j No. 5 j 2949
Retinal Detachment Risk TABLE.
RRs of Developing Retinal Detachment After Pediatric Cataract Surgery According to Various Potential Risk Factors Variable
Type of surgery Lensectomy Lensectomy, anterior vitrectomy Unspecified‡ Posterior capsule Intact Not intact Unspecified‡ Surgical technique Not pars plana Pars plana Surgery for secondary cataract None At least once Etiology Nonhereditary Hereditary Laterality Unilateral Bilateral Primary intraocular lens implantation No Yes Morphology Other Nuclear Secondary intraocular lens implantation No Yes Secondary glaucoma No Yes Surgery for secondary glaucoma No Yes Age at cataract surgery, mo 0–5 6–11 12–23 24–47 ‡48 Trend Surgeon experience ‡50 surgeries
Risk of Retinal Detachment After Pediatric Cataract Surgery Birgitte Haargaard,1,2 Elisabeth W. Andersen,1 Anna Oudin,1 Gry Poulsen,1 Jan Wohlfahrt,1 Morten la Cour,2 and Mads Melbye1 1 2
Department of Epidemiology Research, Statens Serum Institut, Denmark Department of Ophthalmology, Glostrup University Hospital, Copenhagen, Denmark
Correspondence: Birgitte Haargaard, Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen, Denmark; [email protected], [email protected]. Submitted: January 21, 2014 Accepted: March 27, 2014 Citation: Haargaard B, Andersen EW, Oudin A, et al. Risk of retinal detachment after pediatric cataract surgery. Invest Ophthalmol Vis Sci. 2014;55:2947–2951. DOI:10.1167/ iovs.14-13996
PURPOSE. To determine the long-term risk of retinal detachment following pediatric cataract surgery and to identify risk factors for retinal detachment. METHODS. We included all children (aged 0 to 17 years) who during the time period of 1977 to 2005 underwent pediatric cataract surgery in Denmark, excluding cataract cases caused by trauma, or acquired systemic or acquired ocular pathology, and cases with ocular anomalies associated with the development of retinal detachment. Cases of cataract were ascertained from the mandatory Danish National Patient Register, and information on retinal detachment was based on medical chart review. RESULTS. Among 1043 eyes of 656 children undergoing surgery for pediatric cataract, 25 eyes (23 children) developed retinal detachment at a median time of 9.1 years after surgery. The overall 20-year risk of retinal detachment was 7% (95% confidence interval [CI]: 3%–11%) among cataract patients. In otherwise normal children having isolated cataract, the risk was 3% (95% CI: 0%–7%). A significantly higher risk of developing retinal detachment was found in children with mental retardation (23% [95% CI: 9%–35%]) or in cataract cases with other ocular or systemic anomalies (16% [95% CI: 6%–24%]). CONCLUSIONS. The estimated overall risk of retinal detachment 20 years after pediatric cataract surgery was 7%, but only 3% for isolated cataract. Particularly high risks of retinal detachment after cataract surgery were associated with mental retardation and having other ocular or systemic diseases. Keywords: pediatric cataract, retinal detachment, epidemiology
mong adults, it is well-known that the risk of retinal detachment after cataract surgery is higher compared with eyes not undergoing cataract surgery. Thus, studies have reported a 7.5 to 8.7 times higher risk 6 or more years after cataract surgery.1,2 The risk of retinal detachment in adults remains higher even 20 years after cataract surgery.3 Among adults without previous cataract surgery, the overall risk of retinal detachment is estimated to be 0.03% per person year.1 In comparison, the occurrence of retinal detachment among children is very rare. Based on data from the Danish National Patient Register, retinal detachment occurs in approximately 0.001% of all children aged 0 to 17 years (la Cour, unpublished observations, 2008). In children, it is recognized that retinal detachment is a late complication to cataract surgery. The condition has been reported to occur on average 23 to 33 years after the primary surgery,4–6 with around one-third occurring within the first 10 years.4,7 Previous studies on the risk retinal detachment after pediatric cataract surgery have short-term follow-up times (3.5 to 6.8 years) and are based merely on aphakic eyes.8–10 Accordingly, there is a lack of large, long-term studies on the risk of retinal detachment after surgery for pediatric cataract including both pseudophakic and aphakic eyes. It is also unknown if different surgical procedures for pediatric cataract have an influence on the risk of later detachment. Before 1990 in Denmark, the most common cataract surgery was lensec-
A
Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc. www.iovs.org j ISSN: 1552-5783
tomy without posterior capsulorhexis and anterior vitrectomy. After 1990, many surgeons changed surgical technique and included posterior capsulorhexis and anterior vitrectomy as standard procedures in small children undergoing surgery for pediatric cataract. Based on the long existing Danish national registries, we therefore established a population-based cohort of children who had undergone surgery for pediatric cataract during the period of 1977 to 2005. The aim was to evaluate the long-term risk of retinal detachment following pediatric cataract surgery and to look for risk factors for developing retinal detachment in these patients.
METHODS Study Cohort Since 1977, all discharge diagnoses and surgical procedures of patients admitted to public hospitals have been registered in the Danish National Patient Register (NPR). Since 1995 also outpatients have been registered. Based on the information from the NPR, we established a cohort of all children, who were diagnosed with pediatric cataract during the period of 1977 to 2001 before the age of 18 years. We validated the cataract diagnosis by subsequently contacting all relevant hospitals to retrieve and review the children’s medical records. Additional 2947
Retinal Detachment Risk case information was obtained from consultant private ophthalmologists attended by the children. We obtained the complete medical record, including all follow-up visits and consultation data. In Denmark, surgery for retinal detachment is performed only at public hospitals in both children and adults. Information about possible death and emigration was obtained by linkage with the Danish Civil Registration System.11 For this study, only cataract cases (diagnosed between 1977 and 2001) who underwent cataract surgery during the period of 1977 to 2005 were included in the study cohort. Cataract cases caused by trauma, or considered due to acquired systemic (e.g., diabetes) or acquired ocular pathology (e.g., uveitis), were excluded.12,13 We furthermore excluded cataract cases with ocular conditions considered to be highly associated with the development of detachment in itself or after cataract surgery (persistent fetal vasculature [PFV]; neyes ¼ 43) and retinopathy of prematurity (ROP; neyes ¼ 2). Information on retinal detachment following pediatric cataract surgery was obtained from the medical records. Permission to receive data from the national registries was obtained from the Danish Data Protection Agency (2000-410285). The study was approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg ([KF] 01-253/ 00), and it adhered to the tenets of the Declaration of Helsinki.
Follow-up All analyses were based on eyes as the unit. Time at risk was defined for each eye as the time from cataract surgery until time of diagnosis of retinal detachment, date of last visit to an ophthalmologist, emigration or death, date of relevant trauma (neyes ¼ 1), or posterior vitrectomy (neyes ¼ 3), whichever came first. Accordingly, eyes with retinal detachment prior to cataract surgery were not included in the analyses (neyes ¼ 3). The median follow-up time since cataract surgery was 6.8 years (25th quartile, 2.6 years; 75th quartile, 12.8 years).
Statistical Analyses Rate ratios of retinal detachment following surgery of pediatric cataract according to various characteristics were estimated by a Cox proportional hazards regression model with time since surgery as underlying time scale using the procedure PROC PHREG in advanced analytics software (SAS; SAS Institute, Inc., Cary, NC, USA). Age at surgery was analyzed by including age in the regression model with the following categories (in months): 0 to 5, 6 to 11, 12 to 23, 24 to 47, and ‡48 months. A trend was fitted by allowing a linear effect of age at surgery (in months). The outcome for two eyes from the same person can not necessarily be considered independent. The traditional standard errors were therefore substituted by robust standard errors that allows for such a clustered data structure,14 resulting in slightly wider confidence intervals on estimated rate ratios. The cumulative risk of retinal detachment by years since cataract surgery was estimated by Kaplan-Meier estimates using statistical software (Stata 12; StataCorp LP, College Station, TX, USA).
RESULTS During the time period of 1977 to 2005, a total of 1043 eyes of 656 children had a validated diagnosis of pediatric cataract, underwent cataract surgery, and were without other known risk factors for developing retinal detachment (see Methods section). In total, 25 eyes (23 children) with retinal detachment were observed in the study. Median time between cataract surgery
IOVS j May 2014 j Vol. 55 j No. 5 j 2948 and development of retinal detachment was 9.1 years (25th quartile, 5.2; 75th quartile, 16.9 years). Two children developed bilateral retinal detachments. We found only a slight insignificant (P ¼ 0.73) male predominance: 56% (14/25). In the Table, the rate ratios of developing retinal detachment according to possible risk factors are shown. Retinal detachment was significantly higher in eyes of children with mental retardation (rate ratio [RR] ¼ 9.59 [95% CI: 3.89, 23.61], P < 0.001) and in eyes with other ocular or systemic diseases (clinical manifestation; RR ¼ 8.52 [95% CI: 3.28, 22.15], P < 0.001), but also in children having pars plana lensectomy (RR ¼ 4.66 [95% CI: 1.05, 2.63], P ¼ 0.04). However, after adjusting for mental retardation and clinical manifestation, only mental retardation remained significant (RR ¼ 5.26 [95% CI: 1.24, 22.36], P ¼ 0.03), whereas clinical manifestation (RR ¼ 3.39, [95% CI: 0.81, 14.15], P ¼ 0.09) and pars plana surgery (RR ¼ 2.34 [95% CI: 0.38, 14.43], P ¼ 0.36) became insignificant. All other adjusted rate ratios were below 1.7 and insignificant. Due to the higher correlation between mental retardation and clinical manifestation, we investigated their interaction further. No statistically significant interaction was observed (P ¼ 0.43). However, in children without mental retardation, eyes of children having other ocular or systemic diseases had a significantly higher rate of retinal detachment (RR ¼ 4.39 [1.05–18.33], P ¼ 0.04); and in children whose cataract was associated with other ocular or systemic disease, having mental retardation was associated with a significantly higher rate of retinal detachment (RR ¼ 8.12 [1.23–53.48], P ¼ 0.03). RR in eyes in children having both mental retardation and other ocular or systemic diseases compared with children having neither was 14.12 (4.80–1.4), P < 0.001. Due to these additional results, we emphasize in the following both the association with mental retardation and clinical manifestation. Age at surgery did not appear to be associated with risk of retinal detachment. Among children (304 eyes) who received a primary intraocular lens implantation, no cases developed retinal detachment. We also compared surgeons within the present study who had performed more than 50 pediatric cataract surgeries with those having performed less. There was no difference between the two groups on the risk of retinal detachment (RR ¼ 1.24 [95% CI: 1.05, 20.72] P ¼ 0.71). There was no difference in the risk estimates for retinal detachment after cataract surgery performed before 1990 and after 1990 (RR ¼ 1.16 [95% CI: 0.47, 2.89] P ¼ 0.75), when the majority of eyes had primary surgery with posterior capsulorhexis and anterior vitrectomy performed. Figure (A) shows the cumulative risk of retinal detachment by years since cataract surgery. The overall risk of retinal detachment 20 years after pediatric cataract surgery remained 7% (95% CI: 3%, 11%). Including cases with PFV and ROP, the risk was 7% (95% CI: 4%, 11%). Figure (B) shows the cumulative risk of retinal detachment by years since cataract surgery by clinical manifestation. In patients with other ocular or systemic diseases apart from pediatric cataract, the 20-year risk was 16% (95% CI: 6%, 24%) compared with 3% (95% CI: 0%, 7%) in isolated cataract. Figure (C) shows the cumulative risk of retinal detachment by years since cataract surgery by mental retardation. The 20-year risk was 23% (95% CI: 9%, 35%) in patients with mental retardation compared with 3% (95% CI: 0%, 6%) in patients without mental retardation. In 52% (13/25) of the retinal detachment eyes, surgery was not performed because it was considered pointless due to fibrosis. Eight of these eyes had no light perception, two had light perception, one had Snellen visual acuity (VA) of 0.03, one had 0.1, and in one eye, no VA was available.
IOVS j May 2014 j Vol. 55 j No. 5 j 2949
Retinal Detachment Risk TABLE.
RRs of Developing Retinal Detachment After Pediatric Cataract Surgery According to Various Potential Risk Factors Variable
Type of surgery Lensectomy Lensectomy, anterior vitrectomy Unspecified‡ Posterior capsule Intact Not intact Unspecified‡ Surgical technique Not pars plana Pars plana Surgery for secondary cataract None At least once Etiology Nonhereditary Hereditary Laterality Unilateral Bilateral Primary intraocular lens implantation No Yes Morphology Other Nuclear Secondary intraocular lens implantation No Yes Secondary glaucoma No Yes Surgery for secondary glaucoma No Yes Age at cataract surgery, mo 0–5 6–11 12–23 24–47 ‡48 Trend Surgeon experience ‡50 surgeries
