Retinitis pigmentosa (RP) is an inherited retinal disease characterized by progressive loss of the photoreceptors and eventual central visual loss.1 To date, no effective treatment has been discovered to suspend or reverse the degeneration of the photoreceptors; yet, there are different methods to manage the complications of the disease. Cataract is the most common complication of all types of RP. Incidence was reported to be as high as approximately 45%.2 Posterior subcapsular cataract, the most common category, would result in the substantial visual acuity (VA) loss because of direct obscuration of their remaining island of central vision in RP.3 Thus, phacoemulsification with implantation of intraocular lens (IOL) is generally thought necessary for this patient group. However, it is not easy to predict the visual outcomes in consideration of pathological changes in both retina and crystalline lens. Prior to surgery, it is normally difficult to determine whether visual function reduction is due to cataract or the photoreceptor degeneration in RP.
Presently, optical coherence tomography (OCT) has gained wide acceptance in evaluating the retinal structure in vivo.4 OCT emerged as an essential preoperative test in predicting postoperative visual outcomes and risks of complications for patients with age-related cataracts.5 The relationship between the outer retinal disruption on OCT and the outcome of cataract surgery in RP has remained controversial. For example, Yoshida et al.6 found that patients with RP with normal ellipsoid zone (EZ) had better best-corrected VA (BCVA) than those with abnormal EZ. However, Battaglia Parodi et al.7 demonstrated that inner segment / outer segment junction (now named EZ) was not associated with the decrease of BCVA after multivariate regression analysis. Moreover, the relationship between the external limiting membrane (ELM) and outcome remains unknown. A retrospective, observational clinical study was designed on patients with RP who underwent cataract surgery to present more detailed analysis on structural change and its effect on visual outcome. Predictive factors affecting postoperative VA were evaluated in this study.
Patients and Methods
This retrospective case study was conducted on 109 eyes of 70 consecutive patients with RP (43 men and 27 women) who underwent cataract surgery at the Eye Hospital of Wenzhou Medical University (WMU) between October 2010 and January 2016. The age of the patients ranged from 30 years to 74 years (mean: 53.4 years ± 10.3 years). Written informed consent was obtained from all participants, and the study was approved by the institutional review board. The diagnosis of RP was made based on clinical history and physical examination. Any patients with history of vitreoretinal surgery or factors that preclude OCT examinations, including macular edema, vitreomacular traction, glaucoma, high myopia, and dense cataracts, were excluded from this study.
Cataract surgeries were performed by experienced ophthalmologists at the Eye Hospital of WMU who carried out standard phacoemulsification and implantation of IOLs in all patients. All patients had a complete ophthalmic examination including spectral-domain OCT (3D OCT-2000; Topcon, Tokyo, Japan), direct ophthalmoscopy, and BCVA measurements before the surgery. BCVA was measured monocularly at a test distance of 5 months before and 3 months after cataract surgery and expressed in decimal form but stated in logMAR format during statistical analysis.
The appearance of the EZ line in the OCT images at the macular was divided into two groups: discontinuous EZ group (EZ line not visible or discontinuous) and intact EZ group (EZ line continuous). The same method for classification was applied to the ELM line. The classification of the EZ and ELM was made by two of the authors (JBM and DF), who were masked to the BCVA. If there was any discrepancy between primary grading and second grading, the OCT image was submitted to a senior ophthalmologist (LS) for final decision. The central macular thickness (CMT) was measured from the horizontal and vertical cross-sectional images of slices passing through the fovea. Three measurements were made, and the mean of the three was calculated. Subsequently, the data of the vertical and horizontal scans were averaged for each eye. The averaged CMT was divided into two groups: group 1 (CMT < 200 μm) and group 2 (CMT ≥ 200 μm).6
Paired t-tests were used to determine the significance of the changes in the BCVA. The postoperative BCVA in each subgroup was compared using data analyzed by independent-sample t-test. A multiple linear regression analysis was performed using the preoperative BCVA, status of EZ, ELM, and CMT grade as variables to evaluate the impact on postoperative visual prognosis. P value of less than .05 was considered statistically significant.
A total of 109 eyes from 70 subjects (43 men and 27 women) were examined. The age range was 30 years to 74 years, with a mean of 53.4 years. Baseline characteristics of patients with RP are shown in Table 1.
Baseline Characteristics of Patients (n = 70) and Eyes (n = 109) With RP
Changes in preoperative and postoperative BCVA are shown in Figure 1. The mean preoperative BCVA was 0.80 ± 0.59 (range: 0.05 to 2.40). Although it seemed that the postoperative BCVA was significantly improved from the preoperative BCVA (P < .001, paired sample test), the postoperative BCVA was improved (> 0.3 log MAR) in only 52 eyes (47.7%) and was unchanged in 57 eyes (52.3%). Neither of the eyes' postoperative BCVAs were worsened from the baseline. A significant positive correlation was found between preoperative and postoperative BCVA (R = 0.768; P < .001).
Changes in preoperative best-corrected visual acuity (BCVA) and postoperative BCVA. Postoperative BCVA was significantly improved compared with preoperative BCVA (P < .001). logMAR = logarithm of the minimum angle of resolution
External Limiting Membrane
As shown in Figure 2, a standard OCT image was chosen to represent each of the two ELM groups. The ELM was invisible or abnormal (discontinuous ELM group) in 30 eyes (27.5%). In this group, postoperative BCVA was improved in 18 eyes (60.0%). Meanwhile, a normal ELM (intact ELM group) was identified in 79 eyes (72.5%). In this group, postoperative BCVA was improved in 70 eyes (88.6%) (X2 = 11.440; P = .001). The mean postoperative BCVA was 0.85 ± 0.48 in the discontinuous ELM group and 0.30 ± 0.26 in the intact ELM group. A significant difference existed between the mean postoperative BCVA of the two groups (P < .001, independent-samples t-test).
Typical optical coherence tomography macular scan of the external limiting membrane (ELM) of each grade, best-corrected visual acuity (BCVA) of each ELM grade, and percentage of patients with improved BCVA. (A) The ELM was not abnormal (grade 1) in 30 eyes (27.5%) and normal (grade 2) in 79 eyes (72.5%). (B) Postoperative BCVA was significantly better in grade 2 than in grade 1 (P < .001). (C) The percentage of patients whose BCVA improved in grade 1 (60.0%) was significantly different with grade 2 (88.6%). logMAR = logarithm of the minimum angle of resolution
As illustrated in Figure 3, a standard OCT image was chosen to represent each of the two EZ groups. The EZ was invisible or abnormal (discontinuous EZ group) in 33 eyes (30.3%). In this group, the postoperative BCVA was improved in 21 eyes (63.6%). Further, a normal EZ (intact EZ group) was identified in 76 eyes (69.7%). In this group, the postoperative BCVA was improved in 67 eyes (88.2%) (X2 = 8.895; P = .003). The mean postoperative BCVA was 0.80 ± 0.38 in discontinuous EZ group and 0.30 ± 0.32 in the intact ELM group. There was also a significant difference in the mean postoperative BCVA between the two groups (P < .001, independent-samples t-test).
Typical optical coherence tomography macular scan of the ellipsoid zone (EZ) of each grade, best-corrected visual acuity (BCVA) of each EZ grade, and percentage of patients whose BCVA improved. (A) The EZ was abnormal (grade 1) in 33 eyes (30.3%), normal (grade 2) in 76 eyes (69.7%). (B) Postoperative BCVA was significantly better in grade 2 than in grade 1 (P < .001). (C) The percentage of patients whose BCVA had improved in grade 1 (63.6%) was significantly different with grade 2 (88.2%). logMAR = logarithm of the minimum angle of resolution
Central Macular Thickness
There were 51 eyes (46.8%) in group 1 (CMT, < 200 μm), and 58 eyes (53.2%) in group 2 (CMT, ≥ 200 μm). The mean CMT was 192.98 μm ± 31.00 μm in group 1 and 237.84 μm ± 29.85 μm in group 2. The postoperative BCVA was significantly better in group 2 than in group 1 (P < .001, independent-samples t-test). Moreover, the correlation between the CMT and the postoperative BCVA was significant (r= −0.526; P < .0001) (Figure 4).
Plot of postoperative best-corrected visual acuity (BCVA) (logMAR) as a function of central macular thickness (CMT). Correlation between the CMT and the postoperative BCVA (logMAR). The CMT is significantly correlated with the postoperative BCVA (r=−0.510, P < .0001). logMAR = logarithm of the minimum angle of resolution
Multiple Linear Regression
A multiple linear regression analysis was performed using the preoperative logMAR VA, status of EZ, status of ELM, and CMT group as variables to evaluate the impact on postoperative VA (R2 = 0.753; P < .001). The factors that were found to be significantly associated with postoperative BCVA at 3 months were preoperative log MAR VA (P < .001), ELM integrity (P < .001), and CMT group (P = .017). The status of EZ was not significantly correlated (P > .05) (Table 2).
Multiple Linear Regression Analysis for Postoperative LogMAR VA in Patients with RP
The incidence of cataract, one of the most common complications of RP, was reported to be present in approximately 45% of the patients.2 It has been reported that cataracts in patients with RP develop faster than simple age-related cataracts. In the present study, the mean age at surgery in patients with RP is 53.4 years ± 10.27 years, whereas the mean age at surgery in those with age-related cataracts was reported to range from 72 years old to 74 years old.8 With the presence of RP, relatively minor lens opacity may cause disproportionate functional symptoms. Cataract surgery led to an increase of contrast and helped those with RP gain VA. In the present study, we investigated the factors affecting postoperative VA and assessed their predictive value in patients with RP.
In the present study, we found a significant improvement in the mean BCVA after surgery, and no one had a worsening VA. However, only approximately half of the eyes (47.7%) were improved after surgery. This is similar to previous studies,3,6,8,9 which showed that the mean BCVA was significantly improved after surgery: postoperative BCVA was improved in 42% to 87.5% eyes but worsened in none to 2.5% eyes. This illustrates that only a negligibly small percentage of patients with RP have worsened VA after cataract surgery. Additionally, some of the studies pointed out a subjective improvement in function after surgery even when VA remains unchanged. This indicates that the combination of various methods in measuring visual function may better assess visual outcome post-surgery in patients with RP. All the above suggests that cataract surgery was beneficial with respect to VA in most patients with RP. Thus, we recommend cataract surgery as an available choice for patients with RP and cataract.
The EZ is the second hyperreflective band on OCT that corresponds with the anatomical location of the ellipsoid portion of the photoreceptors inner segment.10 In many retinal diseases, including macular hole11–12 and retinal detachment,13 the relationship between the presence of the EZ line and preserved photoreceptor function has been reported. As the early histopathological changes in eyes of patients with RP were a shortening or distortion of the rod and cone photoreceptor outer segments, monitoring the integrity of EZ using OCT can be a valuable indicator to evaluate the structural changes of the outer retina in patients with RP. Accumulative evidence shows that the integrity of EZ is strongly associated with better visual function, brighter fundal autofluorescent parafoveolar density, and higher retinal sensitivity in disease of the outer retina including RP.14–18 Chhablani et al.14 described that the EZ length is significantly correlated with the VA and that the presence of the EZ was associated with better VA in patients with RP. Battu et al.15 also reported that the length of the EZ line correlated with the retinal sensitivity in patients with RP. In the present study, the patients with an intact EZ showed a significantly better VA than those without an intact EZ, representing a potential indicator of retinal function.
The integrity of the ELM line, the discrete hyperreflective band at the outermost border of the outer nuclear layer, was reported to be another potential indicator of retinal function. A relationship between an intact ELM and good visual function has been noted in different retinal diseases, including degenerative eye diseases such as age-related macular degeneration, macular hole, and epiretinal membrane.12,19–22 Iacono et al.20 investigated the relationship between ELM integrity and visual acuity in patients with diabetic macular edema. The mean baseline BCVA was significantly better in eyes with an intact ELM. Our results also showed that patients with an intact ELM line exhibited a remarkably better VA than those without, which is consistent with previous studies.7 In other words, the absence of ELM layers would be associated with a decrease in BCVA in patients with RP. In RP, it is possible that the ELM could be a marker of photoreceptor integrity, which might play an important role in the reorganization of the photoreceptor microstructure.19 To our knowledge, this is the first report on the relationship between the ELM line and VA in patients with RP after cataract surgery.
In patients with advanced RP, it is difficult to identify the border between the retinal layers. Therefore, the use of retinal macular thickness to assess the condition of the retina would be an optimal choice. With careful assessment, a prominently better VA correlates well with a greater macular retinal thickness.23 Clinical studies also implied a correspondence between severe visual field defects and thinner macula thicknesses.24 Additionally, reports showed that retinal thickness corresponds to the amplitude of the focal macular electroretinograms.25 In the present study, it was found that postoperative BCVA was significantly better in group 2 (CMT, ≥ 200 μm) than in group 1 (CMT < 200 μm) (P < .0001, independent-samples t-test), and the correlation between the CMT and the postoperative BCVA was significant (r = −0.526, P < .0001). It is likely that moderate retinal atrophy with thicker retinal thickness was often associated with better visual function. However, few reports demonstrated that eyes with poor VA had maintained relatively normal CMT,26 or eyes with worse VA had accompanied thicker CMT.27 The presence of retinal edema may account for the phenomena of thicker retina with worse VA.28
By using multiple linear regression analysis, we also explored which of the preoperative variables were significant to be predictors of postoperative visual outcome. Among all measurements, preoperative logMAR VA, ELM integrity, and CMT group were essential predictors of BCVA at 3 months. EZ integrity was not significantly associated. However, the status of EZ was individually correlated with postoperative BCVA in the present study, as expected from some previous reports. The layer that is found to contribute more to VA differs from study to study. One reason for this variation may be the deficit order of the layers. Hagiwara et al.29 found that in all subject eyes with RP, the length was the longest in the ELM, followed by the EZ, which suggests that shortening of the ELM is associated with the EZ and that retinal layer may become disorganized first at the EZ line and then the ELM line. This hypothesis was also supported by Liu et al.,28 who concluded that the deficit of the EZ preceded that of the ELM in RP. This indicated that the significance of the association between preoperative retinal layer status and VA may depend on the timing of the measurement.
In conclusion, our study showed that mean postoperative BCVA was significantly improved from preoperative BCVA in approximately half of the eyes after cataract surgery in patients with RP. The preoperative BCVA, the status of ELM, and CMT grade may be important in predicting the BCVA after cataract surgery.
- Oishi A, Oishi M, Ogino K, Morooka S, Yoshimura N. Wide-field fundus autofluorescence for retinitis pigmentosa and cone/cone-rod dystrophy. Adv Exp Med Biol. 2016;854:307–313. doi:10.1007/978-3-319-17121-0_41 [CrossRef]
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Baseline Characteristics of Patients (n = 70) and Eyes (n = 109) With RP
|Characteristics||Patients and Eyes|
|Mean Age (Range), Years||53.4 + 10.27 (30 to 74)|
|Gender, No. of Patients (%)|
| Male||43 (61.4%)|
|EZ, No. of Eyes (%)|
| Not visible or discontinuous||33 (30.3%)|
| Continuous||76 (69.7%)|
|ELM, No. of Eyes (%)|
| Not visible or discontinuous||30 (27.5%)|
| Continuous||79 (72.5%)|
| < 200 um, mean (range); No. of eyes (%)||192.98 + 31.00 um, 51 (46.8%)|
| ≥ 200 um, mean (range); No. of eyes (%)||237.84 + 29.85 um, 58 (53.2%)|
|BCVA (Range); logMAR|
| Mean preoperative BCVA||0.80 + 0.59 (0.05 to 2.40)|
| Mean postoperative BCVA (3m)||0.45 + 0.41 (0.00 to 2.40)|
Multiple Linear Regression Analysis for Postoperative LogMAR VA in Patients with RP
|Multiple Linear Regression Analysisa (n = 109 Eyes)||Coefficient (95% CI)||P Valueb|
|Preoperative logMAR BCVA||0.423 (0.346 to 0.499)||< .001|
|ELM integrity||−0.300 (−0.410 to −0.189)||< .001|
|CMT Group||−0.135 (−0.245 to −0.024)||.017|