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Visual Acuity Outcomes after Cataract Extraction with Intraocular Lens Implantation in Eyes with Diabetic Retinopathy
Journal Pre-proof Visual Acuity Outcomes after Cataract Extraction with Intraocular Lens Implantation in Eyes with Diabetic Retinopathy Michael M. Han, Weilin Song, Thais Conti, Felipe F. Conti, Tyler Greenlee, Grant Hom, Isaac N. Briskin, Rishi P. Singh, Katherine E. Talcott PII:
S2468-6530(19)30690-6
DOI:
https://doi.org/10.1016/j.oret.2019.12.018
Reference:
ORET 687
To appear in:
Ophthalmology Retina
Received Date: 4 October 2019 Revised Date:
26 December 2019
Accepted Date: 27 December 2019
Please cite this article as: Han M.M, Song W., Conti T., Conti F.F, Greenlee T., Hom G., Briskin I.N, Singh R.P & Talcott K.E, Visual Acuity Outcomes after Cataract Extraction with Intraocular Lens Implantation in Eyes with Diabetic Retinopathy, Ophthalmology Retina (2020), doi: https:// doi.org/10.1016/j.oret.2019.12.018. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © YEAR Published by Elsevier Inc. on behalf of American Academy of Ophthalmology
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Visual Acuity Outcomes after Cataract Extraction with Intraocular Lens Implantation in Eyes with Diabetic Retinopathy Michael M Han1, Weilin Song2, Thais Conti3,4, Felipe F Conti3,4, Tyler Greenlee3,4, Grant Hom1,3,4, Isaac N Briskin5, Rishi P Singh1,2,3,4, Katherine E Talcott3,4 Institution: 1. Case Western Reserve University School of Medicine, Cleveland, OH 2. Cleveland Clinic Lerner College of Medicine, Cleveland, OH 3. Cole Eye Institute, Cleveland Clinic, Cleveland, OH 4. Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH 5. Department of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH ePoster accepted for the American Academy of Ophthalmology Annual Meeting, 2019 Conflicts of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Running Head (34/65 characters): Visual Acuity Outcomes after Cataract Surgery in Diabetic Eyes Corresponding Author: Katherine E. Talcott, MD 9500 Euclid Avenue, Desk i30 Cleveland, OH 44195 Phone: (440) 988-4040 Email: [email protected]
1
Abstract (331/350 words)
2
Purpose: To evaluate change in best corrected visual acuity (BCVA) in patients with diabetes
3
and diabetic retinopathy (DR) following cataract extraction (CE).
4
Design: Retrospective cohort study.
5
Subjects: Diabetic eyes of patients aged 18 or older that underwent CE at the Cleveland Clinic
6
from 2013 to 2018.
7
Methods: Chart review examining visual acuities from patient visits before and after surgery, as
8
well as optical coherence tomography (OCT) images. Statistical analysis was done using
9
multiple linear regression models.
10
Main Outcome Measures: Primary endpoint was change in BCVA over the first post-operative
11
year. Secondary endpoint was the association of the central subfield thickness (CST) at baseline
12
with change in BCVA over this same period. Additional pre-operative factors examined were
13
age, race, gender, laterality, insulin use, HbA1c, creatinine, blood urea nitrogen, and estimated
14
glomerular filtration rate.
15
Results: Diabetic eyes without DR (n=138) and eyes with mild/moderate non-proliferative DR
16
(NPDR; n=125), severe NPDR (n=20), and proliferative DR (PDR; n=72) were included. A year
17
after surgery, eyes without DR gained a median of 11.0 [(Q1, Q3), (5.0, 20.0)] ETDRS letters
18
from 65.0 (58.0, 70.0) before surgery, eyes with mild/moderate DR gained 10.0 (5.0, 22.0) from
19
65.0 (58.0, 76.0), eyes with severe NPDR gained 20.5 (8.0, 28.5) from 55.0 (26.0, 65.0), and
20
eyes with PDR gained 15.0 (6.0, 29.5) from 55.0 (35.0, 61.0). Eyes without DR or mild/moderate
21
NPDR had significantly greater improvements in VA a year after surgery as compared to eyes
22
with severe NPDR or PDR when controlling for baseline VA, with more severe retinopathy
23
having less expected visual acuity gain (p<0.001). This effect was not as pronounced for eyes
1
with higher baseline VA before surgery. Length of disease most strongly related to baseline
2
retinopathy severity (ρ=0.431, p<0.001). Baseline retinopathy is a significant driver of VA
3
change post-surgery and significantly interacts with baseline ETDRS.
4
Conclusion:
5
Cataract surgery is beneficial in the majority of patients with diabetic retinopathy without severe
6
concurrent macular pathology. However, pre-operative visual acuity and the severity of diabetic
7
retinopathy can limit visual outcomes.
8
1 2
Background Diabetic retinopathy (DR) is a common and vision threatening complication of diabetes,
3
occurring in a third of patients with diabetes.1 Moreover, patients with diabetes carry an
4
increased risk of developing cataracts.2 Cataract surgery in patients with DR has been shown to
5
improve best corrected visual acuity (BCVA) and significantly improve vision-related quality of
6
life.3 However, those with DR can have poor post-operative visual outcomes and a higher rate of
7
complications compared to those without DR. Complications include diabetic macular edema
8
(DME), post-operative pseudophakic cystoid macular edema, and progression of DR.4–7 Specific
9
risk factors associated with poor outcomes in diabetes have been evaluated and include advanced
10
age, insulin dependence, and elevated HbA1c.8 Few studies have specifically addressed the
11
relationship between stage of DR and post-cataract surgery outcomes. Some studies have shown
12
that diabetic patients without DR or those with non-proliferative DR (NPDR) without macular
13
edema had vision improvement in the majority of patients and higher rates of BCVA
14
improvement compared to those who had NPDR with macular edema.9–11 Another study
15
concluded in a large bioinformatics based analysis that BCVA improved with surgery by an
16
average of 4 lines regardless of DR severity or baseline characteristics.12 However, these studies
17
have not examined visual outcomes following cataract surgery for all stages of DR, including
18
more advanced ones.
19
There is concern that cataract surgery may precipitate the progression of DR, however,
20
studies show mixed results.6,13–16 Groups have reported that surgery increases the risk of DR
21
progression, including that the presence of pre-operative DR, compared to diabetic patients
22
without DR, was a risk factor for progression.13 Another group found significant progression to
23
NPDR in diabetic patients previously without DR but did not find progression to proliferative
1
DR (PDR) or development of DME.6 Finally, pre-operative macular edema and poor renal
2
function were risk factors for worsening of DR following cataract surgery.14 However, other
3
studies have found that cataract surgery was not associated with progression of DR. One group
4
reported that extracapsular cataract surgery does not give rise to progression of DR.15 Others had
5
a more nuanced conclusion, finding progression of DR following cataract surgery but concluded
6
that a considerable proportion of these cases reflected the natural disease course or systemic
7
factors, rather than the influence of surgery.16
8 9
The presence of and management of DME can also impact cataract surgery decisionmaking. In the RISE/RIDE study, DME patients treated with ranibizumab who underwent
10
cataract surgery had an increase of an average of two lines in BCVA from baseline. In addition,
11
BCVA continued to improve slightly on average for months after surgery, supporting against the
12
idea that cataract surgery may accelerate DR/DME progression in the context of treatment.
13
Improvements for patients in the sham group from surgery seemed to be neutralized by initial
14
losses in BCVA due to untreated DME, with a net return to baseline with a combination of sham
15
treatments and surgery.17 Conversely, outer retinal atrophy is an additional concern that could
16
limit visual acuity outcomes in cataract surgery. Once thought to be a result of microvascular
17
damage, new research shows the neurodegeneration may be present and responsible for visual
18
symptoms before the formation of microaneurysms.18
19
Given the discrepancies in the literature regarding visual outcomes after cataract surgery
20
in diabetic patients, this study aims to define the relationship between postoperative visual
21
outcomes and pre-operative DR stage and presence of abnormal retinal thickness. Understanding
22
these patterns will help optimize future strategies for the management of cataracts in patients
23
with diabetes.
1
Methods
2
Study Design
3
A comprehensive retrospective chart review was performed for diabetic eyes undergoing
4
cataract surgery at Cole Eye Institute between September 2012 to September 2018. The study
5
obtained approval from the Cleveland Clinic Institutional Review Board (IRB) and all study
6
related procedures were performed in accordance with the Health Insurance Portability and
7
Accountability Act.
8
Included patients were 18 years or older, had a documented diagnosis of type 1 or 2
9
diabetes, and underwent phacoemulsification cataract surgery. Diabetic eyes were identified by
10
filtering patients with International Classification of Diseases (ICD) 9 and 10 codes for diabetes
11
mellitus and cross-referenced with patients who had received biometry in anticipation of cataract
12
surgery. If patients had surgery on both eyes, the eye that was operated on first was chosen for
13
analysis. Eyes were excluded based on the presence of other vitreoretinal or macular disease that
14
could influence cataract surgery outcome. Patients were also excluded if they missed
15
postsurgical follow-up at either 1 or 12 months or if they had received anti-VEGF (AVF) therapy
16
within the month prior to surgery.
17
Our primary objective was to determine change in VA as measured by Early Treatment
18
Diabetic Retinopathy Study (EDTRS) letters in diabetic eyes categorized by their preoperative
19
level of DR. Diabetic eyes were classified based on their pre-operative clinical diagnostic code in
20
the chart into groups: No DR, Mild/Moderate NPDR, Severe NPDR, and PDR. Pre-operative and
21
postoperative visual outcome data were collected at the pre-operative office visit and at 1- and
22
12-month visits following surgery. Retinopathy severity at the 12-month visit was determined
23
again from clinical diagnostic codes from the chart. Baseline characteristics gathered included
1
age, race, gender, laterality, and insulin dependence at the time of surgery. Lab values recorded
2
included HbA1c, creatinine, blood urea nitrogen, and estimated glomerular filtration rate within
3
3 months of surgery, which were excluded if taken due to acute hospitalization or ED visit. Our
4
secondary objective was to determine change in VA in ETDRS letters following cataract surgery
5
compared to pre-operative retinal thickness on optical coherence tomography (OCT). Patients
6
were divided in quartiles according to Central Subfield Thickness (CST) values on pre-operative
7
OCT, and outcome data was compared between quartiles. The presence of disorganization of the
8
retinal inner layers (DRIL) was evaluated on OCT at each of the time points. We defined DRIL
9
as the loss of distinction on OCT between the ganglion cell-inner plexiform layer complex, inner
10
nuclear layer, or outer plexiform layer independent of other retinal pathology, including macular
11
edema. Single, unmasked graders examined HD 5-line raster images through the macula to make
12
a subjective determination of the presence of DRIL.
13 14 15
Statistical Analysis Statistical analysis was done in SAS software (version 9.4; Cary, NC). Continuous
16
measures were summarized with Median [Q1, Q3], and categorical variables were summarized
17
with frequency (%). Baseline Retinopathy Extent (BRE) is analyzed as an ordered variable.
18
Relationships between continuous measures and BRE are quantified using Spearman’s rank
19
correlation coefficients (Spearman’s rho), and the Mantel-Haenszel test is used as a formal
20
hypothesis test of independence between two variables. Spearman’s rho ranges from -1 to 1,
21
where values closer to 1 (or -1, for a negative relationship) indicate very strong relationships, and
22
values closer to 0 indicate very weak relationships. Relationships between categorical variables
23
(DME (CST>320), Gender, Race, and Insulin Dependence) and BRE are analyzed with Kruskal-
1
Wallis Tests. Linear regression models are used to model change in visual acuity from baseline
2
to 1 month and baseline to 12 months. Outcomes were measured as improvement/change to
3
combat ceiling effect. P-values < 0.05 are considered significant, and are bolded.
1
Results
2 3 4
Patient demographics and baseline characteristics There were 138 eyes with No DR, 125 eyes with Mild/Moderate NPDR, 20 eyes with
5
Severe NPDR, and 72 eyes with PDR included in the analysis. Baseline characteristics and
6
change in VA and macular edema (ME) are presented in Table 1 by Baseline Retinopathy Extent
7
(BRE). Overall, 165 (46.5%) were male, the median age at surgery was 70.0 [(Q1, Q3); (64.0,
8
76.0)] years, median length of disease at surgery was 17.7 (10.4, 25.2) years, and median HbA1c
9
was 7.3 (6.5, 8.6)%. 208 (58.6%) of patients identified as White, 48 (13.5%) as Black, 2 (0.6%)
10
as Asian, 2 (0.6%) as American Indian/Alaska Native, 6 (1.7%) as Multiracial, and 15 (4.2%)
11
patients declined or had unavailable ethnicity data. Of the 124 eyes with OCT, median baseline
12
CST was 256 (231.5, 290.5) µm and 17 (13.7%) had ME.
13
There were significant differences when comparing visual acuity at 1 or 12 months to
14
baseline. A year after surgery, eyes without DR gained a median of 11.0 [(Q1, Q3), (5.0, 20.0)]
15
ETDRS letters from 65.0 (58.0, 70.0) before surgery, eyes with mild/moderate DR gained 10.0
16
(5.0, 22.0) from 65.0 (58.0, 76.0), eyes with severe NPDR gained 20.5 (8.0, 28.5) from 55.0
17
(26.0, 65.0), and eyes with PDR gained 15.0 (6.0, 29.5) from 55.0 (35.0, 61.0). Figure 1 shows
18
the development of visual acuities over time in a box plot. All groups improved significantly
19
from baseline to both 1 and 12 months, but there was loss of significance between 1 month and
20
12 months for eyes with Severe NPDR or PDR (Table 2). The variables that were significantly
21
associated with BRE included ETDRS at all time points (p<0.001), VA change at 1 month
22
following surgery (p=0.0261), age (p<0.001), race (p<0.001), length of disease (p<0.001), and
23
indicators of kidney function [BUN (p<0.02), Creatinine (p<0.001), eGFR (p<0.011)] (Table 1).
1
Of these, the strongest relationship was with length of disease, where there was a moderate
2
relationship with BRE (ρ=0.431) indicating worse DR with longer disease. Age has a weak
3
negative relationship with BRE (ρ= -0.358), where eyes of younger patients had worse DR at
4
presentation. Baseline CST or ME, gender, and VA change at 12 months were not significantly
5
associated with BRE.
6
In terms of progression, 9 (6.5%) eyes with No DR, 3 (2.4%) eyes with Mild/Moderate
7
NPDR, and 5 (4.0%) eyes with Severe NPDR showed progression of diabetic retinopathy at 12
8
months. Only 1 (0.7%) of eyes with No DR at baseline ended up receiving injection with anti-
9
VEGF agents over the year due to progression and development of ME; otherwise, 8 (6.4%) of
10
Mild/Moderate NPDR eyes, 10 (50.0%) of Severe NPDR eyes, and 12 (16.7%) of PDR eyes
11
received injections. 0 (0%) of No DR eyes, 10 (17.2%) of Mild/Moderate NPDR eyes, 2 (16.7%)
12
of Severe NPDR eyes, and 5 (14.7%) of PDR eyes had macular edema on OCT at baseline. 0
13
(0%) No DR eyes, 9 (39.1%) Mild/Moderate NPDR eyes, 7 (53.8%) Severe NPDR eyes, and 7
14
(26.9%) PDR eyes had macular edema on OCT at post-operative month 1. 2 (25%) No DR eyes,
15
8 (22.2%) Mild/Moderate NPDR eye, 6 (46.2%), Severe NPDR eyes, and 11 (27.5%) PDR eyes
16
had macular edema on OCT at 12 months. 10 (19.6%) of eyes with non-insulin dependent
17
diabetes mellitus (NIDDM) had disorganization of the inner retinal layers (DRIL) compared to
18
23 (31.5%) of eyes with insulin dependent diabetes mellitus at baseline. At 1 month, 6 (33.3%)
19
of NIDDM eyes had subjective signs of DRIL as compared to 24 (49.0%) of IDDM eyes on
20
OCT. At 12 months, 10 (33.3%) of NIDDM eyes had subjective signs of DRIL as compared to
21
33 (49.3%) of IDDM eyes on OCT.
22 23
Linear regression models for change in visual acuity
1
Baseline variables that were significantly associated with degree of vision recovered
2
following cataract surgery included age, BRE, and EDTRS (Table 3). For every additional year
3
older an eye is at surgery, VA change from baseline to POM 12 decreased by 0.20 letters for that
4
eye (p=0.008). BRE was also a significant driver of VA change post-surgery. At 12 months, eyes
5
with Mild/Moderate NPDR had worse VA change than eyes with No DR by 10.55±9.41 letters
6
(p=0.028); this number increased to 31.35±13.68 (p<0.001) and 30.82±9.60 (p<0.001) for Severe
7
NPDR and PDR eyes respectively.
8 9
Baseline ETDRS and its interaction with BRE indicated that the effect of baseline ETDRS was different for each level of BRE. For patients with No DR, each additional letter of
10
worse ETDRS at baseline resulted in a 0.88 letter VA improvement at POM 12. For
11
Mild/Moderate NPDR eyes, every additional letter of worse ETDRS at baseline resulted in a
12
0.13 diminished letter change compared to the No DR group (p=0.07), and an overall 0.75 letter
13
VA improvement at POM 12. For Severe NPDR eyes, every additional letter of worse baseline
14
ETDRS resulted in a 0.46 diminished letter change compared to the No DR group (p<0.001), and
15
an overall 0.42 letter VA improvement. For PDR eyes, every additional letter of worse baseline
16
ETDRS results in a 0.37 diminished letter change compared to No DR (p<0.001) and an overall
17
0.45 letter VA improvement. These result estimates are shown in Figure 2.
18
While HbA1c, BUN, creatinine, and eGFR were associated with baseline DR severity,
19
they were not independently associated with changes in visual outcome following cataract
20
surgery (Table 3). Table 4 illustrates linear regression results for eyes that had pre-operative
21
OCTs (n=124). Upon preliminary inspection of the CST distribution, it was found that the
22
relationship with VA change was not linear, and CST was thus broken up into quartiles. Eyes
23
with baseline CST between 257 and 289 µm see a higher VA improvement POM 1 than eyes
1
with CST below 231.5 µm by about 7.75 letters. Baseline CST is not a significant driver of VA
2
at POM 12.
3
Using the results, nomograms were constructed from our models to attempt to predict
4
outcomes of cataract surgery in diabetic patients. One such nomogram in Figure 3 includes a
5
demonstration of how to use this tool to predict visual acuity outcome in a particular patient.
6 7 8 9 10
Surgical complication rate Three eyes had complications at the time of cataract surgery. One eye without retinopathy had posterior capsular rupture and suprachoroidal hemorrhage during surgery. The eye ended up with visual acuity 20/200 at one year from baseline 20/60.
11
Another eye with PDR had visually significant retained cortical material that was
12
removed in a subsequent surgery without incident with a final visual acuity of 20/30. Finally, an
13
eye with PDR developed a posterior capsular rupture and vitreous hemorrhage later managed
14
with retinal surgery and had a visual acuity of 20/60.
15
1 2
Discussion Our study characterized the outcomes of cataract surgery in diabetic patients, stratifying
3
them by retinopathy stage, and examining baseline clinical and OCT characteristics to help
4
predict visual improvement. We found that regardless of BRE, patients had a significant gain in
5
visual acuity at POM 12 although these gains were greater for patients without DR or with
6
mild/moderate NPDR as compared to severe NPDR and PDR patients. We found that the visual
7
acuity gains at POM 12 was associated with age, baseline vision and retinopathy stage but not
8
associated with gender, race, insulin dependence, HbA1c, or renal function. The presence of
9
abnormal macular thickness preoperatively was overall not significantly predictive of visual
10
outcomes. We found some progression of diabetic retinopathy in our patient population but not
11
as much as other studies. Our study is the first, as far as we can tell, to attempt to estimate
12
improvement accounting for baseline characteristics, especially baseline visual acuity and
13
retinopathy severity, in a diabetic patient population.
14
We found that baseline visual acuity is a strong predictor of visual acuity gain, which is
15
in line with prior studies. Chew et. al. observed that a pre-operative VA worse than 20/100 had
16
an odds ratio of 8.7 of being unable to achieve a VA of 20/100, while being worse than 20/400
17
had a 12.6 odds ratio, but these were not stratified by retinopathy severity.19 Liu et. al. also
18
described a modest correlation of preoperative VA, diabetes, and diabetic retinopathy in general
19
with a lower probability of achieving a VA greater than 20/25.12 In our study, lower visual
20
acuities were correlated with visual acuity gains, with eyes with more severe retinopathy gaining
21
the most. This may be due to the fact that eyes with Severe NPDR or PDR presented with lower
22
baseline visual acuity, and therefore had more potential for improvement. This is not
23
incompatible with the studies mentioned above, as we can see from our data that VA gain is
1
additionally limited by BRE when outcomes are controlled for baseline VA. Reduced returns of
2
VA gain at lower baseline ETDRS were especially true for these eyes with Severe NPDR and
3
PDR in our study, even when accounting for ceiling effect of patients improving to 20/20 vision,
4
indicating that retina pathology may limit improvement. Nevertheless, the degree of
5
improvement of most eyes with this severity seem to suggest these eyes tended to have worse
6
cataract, and may have had surgery delayed due to providers’ unfavorable expectations of
7
improvement or to prioritize optimizing systemic and/or ocular disease. These patients may also
8
have presented for ophthalmic care with more mature cataracts than other patients. For example,
9
these patients may have more severe renal involvement in their diabetes that may complicate
10 11
scheduling surgery.20 Indeed, all groups showed significant improvement with cataract extraction despite level
12
of BRE, indicating the net positive impact of surgery, which has been demonstrated in multiple
13
studies showing improvement in the vast majority of patients.10,12,21–23 This is consistent with the
14
fact that VA before surgery is a cumulative representation of pathology of the visual axis,
15
including the lens and the retina. In addition, PDR eyes seemed to fare better than eyes with
16
Severe NPDR a year after surgery. This could be due to higher prevalence of prior treatment
17
with PRP in this group with better control of retinal disease before cataract surgery. Chew et. al.
18
showed as much of a 15% increase in probability of gaining more than 2 lines from surgery
19
compared to eyes that deferred PRP in a study of 270 eyes with more severe retinopathy.19
20
Quiescent disease could also explain why the PDR group had prevalence of ME closer to the
21
Mild/Moderate NPDR group during the follow-up period. Considering this, it seems that eyes
22
with appropriate management of retinopathy and undergoing cataract surgery have a favorable
23
prognosis despite retinopathy severity.
1
Eyes with more severe retinopathy who underwent cataract surgery were also younger. as
2
potentially uncontrolled blood sugars can precipitate cataract formation.4 Despite this, being
3
older also negatively affected the outcome of cataract surgery, consistent with previous literature
4
stating worst outcomes in older patients with no ocular comorbities.24 Eyes with severe
5
retinopathy were much more likely to belong to black patients, reflecting a disparity of disease
6
control in this population compared to non-Hispanic whites, but race by itself did not affect
7
visual acuity outcomes.25 Length of disease, insulin dependence, HbA1c, and
8
BUN/Creatinine/eGFR, while significantly worse overall with increasing DR, did not show a
9
completely linear relationship and did not correlate well with visual acuity outcomes. The
10
increased length of disease duration in patients with Mild/Moderate NPDR may reflect tendency
11
for better glycemic control in this patient population. Alternatively, this may be due to patients
12
with Severe NPDR being diagnosed by symptomatic manifestations including vision loss, rather
13
than diagnosed on screening tests, but this group was limited in power. Eyes with PDR tended to
14
present disproportionately later in the disease course and often were quiescent with some degree
15
of PRP before cataract surgery. Laboratory markers like HbA1c, BUN, Creatinine, and eGFR are
16
known fluctuate depending on factors like recent sugar control and hydration status, which could
17
affect their value in predicting visual acuity outcomes. Lower HbA1c values in the Severe NPDR
18
group could also be explained by the more severe renal impairment in this group, as lower eGFR
19
is associated with higher blood insulin levels.26
20
Rate of progression of retinopathy after surgery in our study was lower than in other
21
studies, with the Severe NPDR group having the highest rate of progression at 15%. Many
22
smaller studies have found high rates of progression compared to fellow non-operative
23
eyes.5,9,14,27 However, Wagner et. al. found that only 18.4% of eyes progressed compared to
1
14.3% of non-operative eyes in the first six months in a study of 223 patients, and this difference
2
ultimately disappeared after a period of observation.21 As Parness et. al. observed that 84% of
3
progression occurs in the first 6 months after surgery, this may be a transient worsening that
4
ultimately falls in line with the fellow eye.13 It may also reflect improved visualization of the
5
fundus on exam after cataract surgery. Another large study by Chew et. al. interpreted this
6
difference in progression as of borderline significance (p=0.03).19 The largest study by Jeng et.
7
al. observed a hazard ration of 1.48 for developing background DR but no difference in
8
progressing to PDR.6 Some studies postulated that HbA1c could predict progression, like Hong
9
et. al. who found that patients who progressed had higher average HbA1c of 8.0% vs. the 7.0%
10
of those who did not in their study of 169 patients.5 Parness et. al. similarly found less
11
progression in patients with an HbA1c of 7.5%, and Henricsson et. al. in their study of 70
12
eyes.13,22 However, Kato et. al. did not find such association, albeit in a smaller study of 66
13
patients.16 While our overall low rates of progression could therefore be explained by the lower
14
HbA1c values in our patient population, our Severe NPDR group progressed the most but had
15
lower HbA1c values than our other retinopathy groups. Maculopathy may be an important
16
predictor of progression as well, as Chiu et. al. found in their study of 107 operative eyes that
17
50% of these eyes progressed in DR severity.9
18
We observed higher rates of macular edema both at 1 month (as expected in
19
pseudophakic edema) and higher rates of persistent or recurrent macular edema at 12 months in
20
eyes with worse retinopathy, especially in eyes with Severe NPDR. Unlike progression of
21
retinopathy, our rates of macular edema agreed more with smaller studies done on the subject,
22
but our observations were only based on patients who received OCT at their follow-up visits. For
23
example, Parness et. al. found that 50% of their operative eyes developed DME, Krepler found
1
31% development compared to 13.5% in non-operative eyes in a study of 50 patients, and
2
Pollack found a rate of 39% in their 33 eyes.10,13,27 The largest of these studies by Chu et. al. of
3
over 81,984 patients found an 1.80 relative risk of developing post-operative macular edema
4
within 90 days of surgery in diabetics in general.7 However, they also observed much higher
5
rates of edema with other ocular comorbidities like capsular rupture, epiretinal membrane,
6
uveitis, retinal vein occlusion, and retinal detachment repair, some of which share risk factors
7
with diabetes. While many of these studies reflected pseudophakic macular edema worsened by
8
diabetes, Kutschan et. al. used a longer follow-up period to determine that rates of likely DME
9
were ultimately 6.8% at 19 months and persistent at 6.7% at 38 months, which were likely not
10
reflective of cataract surgery.15 Chu et. al. supported these findings as well, observing no long
11
term persistence of macular edema in operative vs. non-operative eyes.19
12
We used these findings to help prognosticate the amount of vision recovered in eyes with
13
cataract and diabetic retinopathy as their principle pathologies. As mentioned above, studies
14
prior often used thresholds of visual acuity to prognosticate vision, which could run the risk of
15
under or over-estimating the visual prognosis of patients who are subsequently categorized. The
16
nomogram built from the models included in this study could aid in clinical decision making of
17
when it would be beneficial for patients to have cataract surgery and setting realistic visual
18
expectations post-operatively. For example, it could be used to determine if surgery may
19
improve vision enough to allow a patient to drive according to the laws of their state.
20
This study had several limitations. Surgeons generally chose the eye with worse visual
21
acuity or more significant cataract to undergo phacoemulsification first, which often selected for
22
eyes with more guarded prognosis, or alternatively, more visual gain potential. Regardless, there
23
is selection bias as these were patients who were already clinically assessed as good surgical
1
candidates. For instance, they might not reflect all patients with diabetic retinopathy and
2
cataracts, including patients with diabetic complications such as tractional retinal detachments or
3
severe diabetic macular edema. There was therefore a relatively small sample of eyes with more
4
advanced DR, including Severe NPDR and PDR. The retrospective nature of this study limited
5
these numbers but the relatively low numbers of more advanced DR may also reflect some bias
6
in who was referred for cataract surgery. We measured lower rates of progression compared to
7
other studies but did not have fundus photographs on record to compare severe pre-operatively
8
vs. 12 months post-operatively, as some studies did.5 Additionally, a minority of eyes with OCT
9
at baseline had macular edema, which greatly limited our analysis, and subsequent OCTs were
10
not consistently done in the same patients. There may have been significant selection bias in
11
included OCTs as these tests were more frequently done in patients who had clinical findings
12
suspicious for macular edema. Patients with known DME may also have been less likely to be
13
referred for cataract surgery given concern of cataract surgery worsening the edema and concern
14
for visual potential. Our determination of DRIL was also not as rigorous as other studies which
15
used multiple, masked graders, and which attempted to quantify DRIL using micron
16
measurements or by dividing the central 1mm scan into multiple zones.28,29 We also excluded
17
patients who had intravitreal injections within the month prior to cataract surgery—those with
18
clinical diabetic macular edema who were receiving treatment would have been more likely to be
19
excluded given this.
20
Additionally, many of our patients were missing pre-operative laboratory data, and often
21
these tests were not collected for the purpose of pre-operative evaluation. This may have limited
22
the power of associating these factors to visual acuity outcomes. These factors do not seem to
23
have prognostic value on the surgery itself, which can be explained by the short time frames for
1
which these values had clinical utility. Given the safety of routine cataract surgery and lack of
2
need for general anesthesia, many of these tests have since been excluded from pre-operative
3
assessment.30
4
Cataract surgery could also lend itself to other complications for eyes with more severe
5
DR. While complications like vitreous hemorrhage, tractional retinal detachment, and post-
6
operative macular edema are generally treatable with surgery or intravitreal and topical therapies,
7
damage to the retina is generally irreversible.31 While our study saw immediate complications in
8
only 3 patients, we did not track the development of other complications over the course of the
9
first post-operative year.
10
In conclusion, cataract surgery is beneficial in the majority of patients with diabetic
11
retinopathy without severe concurrent macular pathology. However, visual acuity before surgery
12
and the severity of diabetic retinopathy can limit desired operative outcomes. Clinical judgment
13
of risks and benefits in cataract surgery is therefore complicated by diabetic disease and warrants
14
further consideration of outcomes. Further studies are needed to be understand how other
15
baseline clinical and imaging characteristics can help shape visual outcomes after cataract
16
surgery.
17
1
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Babiuch AS, Han M, Conti FF, Wai K, Silva FQ, Singh RP. Association of Disorganization of Retinal Inner Layers with Visual Acuity Response to Anti-Vascular
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Occlusion. In: JAMA Ophthalmology. ; 2019. doi:10.1001/jamaophthalmol.2018.4484
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200107000-00029
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Das A, Stroud S, Mehta A, Rangasamy S. New treatments for diabetic retinopathy. Diabetes, Obes Metab. 2015. doi:10.1111/dom.12384
1
Figure 1. Visual acuity in diabetic patients undergoing cataract surgery
2 3 4
Figure 2. Visual Acuity gain estimates per Baseline Retinopathy Extent group according to Table 3
5
1
Figure 3. Nomogram Modeling Change in Visual Acuity, Baseline to 12 Months
2 3 4 5 6
Characteristics of the patient eye can be added to the nomogram to predict visual acuity gain at 12 months. For example, a 60 year old non-insulin dependent male patient with an eye with mild/moderate non-proliferative diabetic retinopathy and a baseline visual acuity of 55 letters would be expected to gain 23 letters of visual acuity after surgery.
Table 1. Data according to Baseline Retinopathy Extent
Factor
None (N=138)
Mild/ Moderate NPDR (N=125)
Severe NPDR (N=20)
PDR (N=72)
Spearman pCorrelation value
Baseline CST*, Median µm [Q1, Q3] 240.5[230.0,256.0] 263.5[236.0,300.0] 273.5[223.0,301.5] 257.5[228.0,309.0] 0.089 0.326d Baseline ME (CST>320)*, No. (%) 0/20(0%) 10/58(17.2%) 2/12(16.7%) 5/34(14.7%) 0.275b ME at 1 month, No. (%) 0/5(0%) 9/23(39.1%) 7/13(53.8%) 7/26(26.9%) 0.133b ME at 12 months, No. (%) 2/8(25%) 8/36(22.2%) 6/13(46.2%) 11/40(27.5%) 0.433b ETDRS Baseline, Median letters [Q1, Q3] 65.0[58.0,70.0] 65.0[58.0,76.0] 55.0[26.0,65.0] 55.0[35.0,61.0] -0.287 <0.001d ETDRS 1 month, Median letters [Q1, Q3] 76.0[70.0,80.0] 76.0[70.0,80.0] 73.0[56.5,80.0] 70.0[56.5,76.0] -0.243 <0.001d ETDRS 12 months, Median letters [Q1, Q3] 80.0[76.0,85.0] 80.0[70.0,85.0] 70.0[63.0,80.0] 70.0[61.0,80.0] -0.304 <0.001d VA Change 1 month, Median letters [Q1, Q3] 10.0[4.0,15.0] 10.0[0.00,20.0] 15.0[3.0,41.5] 15.0[5.5,26.0] 0.118 0.0261d VA Change 12 months, Median letters [Q1, Q3] 11.0[5.0,20.0] 10.0[5.0,22.0] 20.5[8.0,28.5] 15.0[6.0,29.5] 0.090 0.091d Age, Median years [Q1, Q3] 72.0[67.0,79.0] 70.0[65.0,77.0] 69.5[63.0,73.0] 62.5[56.0,68.5] -0.358 <0.001d Gender, No. (%) 0.311b Male 56(40.6) 62(49.6) 9(45.0) 38(52.8) Female 82(59.4) 63(50.4) 11(55.0) 34(47.2) Race, No. (%) <0.001b White 104(75.4) 93(74.4) 1(5.0) 10(13.9) Black 34(24.6) 32(25.6) 19(95.0) 62(86.1) Length of Disease*, Median years [Q1, Q3] 8.4[4.2,16.4] 17.5[11.6,22.2] 13.8[4.2,23.2] 24.6[19.5,40.2] 0.431 <0.001d Insulin Dependence, No. (%) 37(26.8) 71(56.8) 11(55.0) 57(79.2) <0.001b HbA1c (within 3 mo. of surgery)*, Median % [Q1, Q3] 6.9[6.3,8.0] 7.6[6.8,9.0] 7.0[6.1,9.3] 7.7[6.9,8.9] 0.210 0.002d BUN*, Median mg/dL [Q1, Q3] 17.0[13.0,23.0] 18.5[15.0,23.0] 33.0[25.0,54.0] 19.0[16.0,27.0] 0.209 0.002d Creatinine*, Median mg/dL [Q1, Q3] 0.98[0.79,1.2] 0.98[0.81,1.3] 1.8[1.2,3.3] 1.2[0.84,1.7] 0.236 <0.001d eGFR*, Median mL/min [Q1, Q3] 60.0[57.0,60.0] 60.0[54.0,60.0] 38.0[15.0,60.0] 60.0[42.0,60.0] -0.174 0.011d * Data not available for all subjects. Missing values: Baseline CST = 231, Length of Disease = 285, HbA1c (within 3 mo. of surgery) = 141, BUN = 138, Creatinine = 136, eGFR = 140. p-values: b=Kruskal-Wallis test, c=Pearson's chi-square test, d=Mantel-Haenszel Trend test. CST = Central Subfield Thickness, ME = Macular Edema, ETDRS = Early Treatment of Diabetic Retinopathy Study, VA = Visual Acuity, BUN = Blood Urea Nitrogen, eGFR = estimated Glomerular Filtration Rate, NPDR = Non-Proliferative Diabetic Retinopathy, PDR = Proliferative Diabetic Retinopathy, CI = Confidence Interval.
Table 2. Difference in ETDRS Letters in Visual Acuity between visits by Baseline Retinopathy Extent Baseline to 1 month Baseline to 12 months Estimates 95% CI p-value Estimates 95% CI No DR 13.2 (10.0-16.4) 16.4 (13.3-19.6) <0.0001 Mild/Moderate NPDR 12.6 (9.4-16.5) 16.0 (12.8-19.3) <0.0001 Severe NPDR 20.6 (10.2-31.0) 21.5 (12.8-30.2) 0.0027 PDR 17.3 (13.3-21.3) 19.0 (14.0-23.9) <0.0001
p-value <0.0001 <0.0001 0.0008 <0.0001
Estimates 3.2 3.1 0.9 1.7
1 to 12 months 95% CI (1.9-4.5) (1.5-4.7) (-6.0-7.8) (-2.4-5.8)
p-value 0.0004 0.0064 0.8273 0.2867
Table 3. Regression Results: Modeling Change in VA Condition Intercept Age (years) Gender: Female (vs Male) Race: Black (vs White) Baseline ETDRS (letters) Insulin Dependence: Yes (vs No) Baseline Retinopathy Extent: Mild/Moderate NPDR (vs None) Severe NPDR (vs None) PDR (vs None) Baseline ETDRS*Baseline Retinopathy Extent Mild/Moderate NPDR (vs None) Severe NPDR (vs None) PDR (vs None) HbA1c (%) BUN (mg/dL) Creatinine (mg/dL) eGFR (mL/min)
Baseline to 1 Month Estimates 95% CI 80.43 67.74 93.11 -0.2 -0.35 -0.05 -1.38 -3.88 1.13 1.55 -1.48 4.58 -0.84 -0.95 -0.73 -1.83 -4.55 0.89
p-value <0.001 0.009 0.282 0.314 <0.001 0.187
Baseline to 12 Months Estimates 95% CI 86.46 73.79 99.12 -0.2 -0.35 -0.05 -1.66 -4.16 0.85 -0.04 -3.06 2.99 -0.88 -0.99 -0.78 0.46 -2.25 3.18
p-value <0.001 0.008 0.194 0.982 <0.001 0.738
-4.09 -20.22 -29.19
-13.51 -33.93 -38.81
5.33 -6.5 -19.57
0.393 0.004 <0.001
-10.55 -31.35 -30.82
-19.96 -45.03 -40.42
-1.15 -17.66 -21.22
0.028 <0.001 <0.001
0.04 0.27 0.39 -0.97 -0.11 -0.6 -0.07
-0.1 0.02 0.23 -2.09 -0.38 -2.54 -0.29
0.19 0.53 0.56 0.15 0.15 1.34 0.16
0.57 0.038 <0.001 0.088 0.41 0.544 0.555
0.13 0.46 0.37 -0.68 0.23 0.71 0.05
-0.01 0.21 0.21 -1.76 -0.03 -1.16 -0.16
0.28 0.72 0.54 0.4 0.48 2.59 0.27
0.07 <0.001 <0.001 0.215 0.081 0.454 0.639
Table 4. Regression Results: Modeling Change in VA – OCT Group Baseline to 1 month Condition Estimates 95% CI Intercept 74.28 59.09 89.47 Baseline ETDRS (letters) -1.02 -1.26 -0.78 Baseline Retinopathy Extent: Mild/Moderate NPDR (vs None) -13.41 -32.94 6.13 Severe NPDR (vs None) -28.45 -50.23 -6.67 PDR (vs None) -40.61 -59.02 -22.2 Baseline CST Quartiles (µm) Q2 [232 to 256] (vs Q1, less than 231.5) 3.3 -2.79 9.39 Q3 [257 to 289] (vs Q1, less than 231.5) 7.75 1.83 13.67 Q4 [290 to 445] (vs Q1, less than 231.5) -0.51 -6.4 5.38 Baseline ETDRS*Baseline Retinopathy Extent Mild/Moderate NPDR (vs None) 0.18 -0.13 0.48 Severe NPDR (vs None) 0.41 0.03 0.8 PDR (vs None) 0.61 0.3 0.92
p-value <0.001 <0.001
Baseline to 12 months Estimates 95% CI p-value 79.67 65.95 93.4 <0.001 -1.06 -1.28 -0.85 <0.001
0.177 0.011 <0.001
-26.68 -53.97 -58.4
-44.32 -73.65 -75.03
-9.03 -34.29 -41.77
0.003 <0.001 <0.001
0.286 0.011 0.865
2.89 3.97 -0.79
-2.62 -1.38 -6.11
8.39 9.31 4.54
0.301 0.145 0.77
0.247 0.035 <0.001
0.4 0.85 0.94
0.12 0.5 0.66
0.67 1.2 1.22
0.005 <0.001 <0.001
Eyes with severe non-proliferative or proliferative diabetic retinopathy had less visual acuity improvement after cataract surgery compared to other diabetic eyes in a study of 355 cases, especially if they had worse preoperative visual acuity.
S2468-6530(19)30690-6
DOI:
https://doi.org/10.1016/j.oret.2019.12.018
Reference:
ORET 687
To appear in:
Ophthalmology Retina
Received Date: 4 October 2019 Revised Date:
26 December 2019
Accepted Date: 27 December 2019
Please cite this article as: Han M.M, Song W., Conti T., Conti F.F, Greenlee T., Hom G., Briskin I.N, Singh R.P & Talcott K.E, Visual Acuity Outcomes after Cataract Extraction with Intraocular Lens Implantation in Eyes with Diabetic Retinopathy, Ophthalmology Retina (2020), doi: https:// doi.org/10.1016/j.oret.2019.12.018. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © YEAR Published by Elsevier Inc. on behalf of American Academy of Ophthalmology
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Visual Acuity Outcomes after Cataract Extraction with Intraocular Lens Implantation in Eyes with Diabetic Retinopathy Michael M Han1, Weilin Song2, Thais Conti3,4, Felipe F Conti3,4, Tyler Greenlee3,4, Grant Hom1,3,4, Isaac N Briskin5, Rishi P Singh1,2,3,4, Katherine E Talcott3,4 Institution: 1. Case Western Reserve University School of Medicine, Cleveland, OH 2. Cleveland Clinic Lerner College of Medicine, Cleveland, OH 3. Cole Eye Institute, Cleveland Clinic, Cleveland, OH 4. Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH 5. Department of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, OH ePoster accepted for the American Academy of Ophthalmology Annual Meeting, 2019 Conflicts of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Running Head (34/65 characters): Visual Acuity Outcomes after Cataract Surgery in Diabetic Eyes Corresponding Author: Katherine E. Talcott, MD 9500 Euclid Avenue, Desk i30 Cleveland, OH 44195 Phone: (440) 988-4040 Email: [email protected]
1
Abstract (331/350 words)
2
Purpose: To evaluate change in best corrected visual acuity (BCVA) in patients with diabetes
3
and diabetic retinopathy (DR) following cataract extraction (CE).
4
Design: Retrospective cohort study.
5
Subjects: Diabetic eyes of patients aged 18 or older that underwent CE at the Cleveland Clinic
6
from 2013 to 2018.
7
Methods: Chart review examining visual acuities from patient visits before and after surgery, as
8
well as optical coherence tomography (OCT) images. Statistical analysis was done using
9
multiple linear regression models.
10
Main Outcome Measures: Primary endpoint was change in BCVA over the first post-operative
11
year. Secondary endpoint was the association of the central subfield thickness (CST) at baseline
12
with change in BCVA over this same period. Additional pre-operative factors examined were
13
age, race, gender, laterality, insulin use, HbA1c, creatinine, blood urea nitrogen, and estimated
14
glomerular filtration rate.
15
Results: Diabetic eyes without DR (n=138) and eyes with mild/moderate non-proliferative DR
16
(NPDR; n=125), severe NPDR (n=20), and proliferative DR (PDR; n=72) were included. A year
17
after surgery, eyes without DR gained a median of 11.0 [(Q1, Q3), (5.0, 20.0)] ETDRS letters
18
from 65.0 (58.0, 70.0) before surgery, eyes with mild/moderate DR gained 10.0 (5.0, 22.0) from
19
65.0 (58.0, 76.0), eyes with severe NPDR gained 20.5 (8.0, 28.5) from 55.0 (26.0, 65.0), and
20
eyes with PDR gained 15.0 (6.0, 29.5) from 55.0 (35.0, 61.0). Eyes without DR or mild/moderate
21
NPDR had significantly greater improvements in VA a year after surgery as compared to eyes
22
with severe NPDR or PDR when controlling for baseline VA, with more severe retinopathy
23
having less expected visual acuity gain (p<0.001). This effect was not as pronounced for eyes
1
with higher baseline VA before surgery. Length of disease most strongly related to baseline
2
retinopathy severity (ρ=0.431, p<0.001). Baseline retinopathy is a significant driver of VA
3
change post-surgery and significantly interacts with baseline ETDRS.
4
Conclusion:
5
Cataract surgery is beneficial in the majority of patients with diabetic retinopathy without severe
6
concurrent macular pathology. However, pre-operative visual acuity and the severity of diabetic
7
retinopathy can limit visual outcomes.
8
1 2
Background Diabetic retinopathy (DR) is a common and vision threatening complication of diabetes,
3
occurring in a third of patients with diabetes.1 Moreover, patients with diabetes carry an
4
increased risk of developing cataracts.2 Cataract surgery in patients with DR has been shown to
5
improve best corrected visual acuity (BCVA) and significantly improve vision-related quality of
6
life.3 However, those with DR can have poor post-operative visual outcomes and a higher rate of
7
complications compared to those without DR. Complications include diabetic macular edema
8
(DME), post-operative pseudophakic cystoid macular edema, and progression of DR.4–7 Specific
9
risk factors associated with poor outcomes in diabetes have been evaluated and include advanced
10
age, insulin dependence, and elevated HbA1c.8 Few studies have specifically addressed the
11
relationship between stage of DR and post-cataract surgery outcomes. Some studies have shown
12
that diabetic patients without DR or those with non-proliferative DR (NPDR) without macular
13
edema had vision improvement in the majority of patients and higher rates of BCVA
14
improvement compared to those who had NPDR with macular edema.9–11 Another study
15
concluded in a large bioinformatics based analysis that BCVA improved with surgery by an
16
average of 4 lines regardless of DR severity or baseline characteristics.12 However, these studies
17
have not examined visual outcomes following cataract surgery for all stages of DR, including
18
more advanced ones.
19
There is concern that cataract surgery may precipitate the progression of DR, however,
20
studies show mixed results.6,13–16 Groups have reported that surgery increases the risk of DR
21
progression, including that the presence of pre-operative DR, compared to diabetic patients
22
without DR, was a risk factor for progression.13 Another group found significant progression to
23
NPDR in diabetic patients previously without DR but did not find progression to proliferative
1
DR (PDR) or development of DME.6 Finally, pre-operative macular edema and poor renal
2
function were risk factors for worsening of DR following cataract surgery.14 However, other
3
studies have found that cataract surgery was not associated with progression of DR. One group
4
reported that extracapsular cataract surgery does not give rise to progression of DR.15 Others had
5
a more nuanced conclusion, finding progression of DR following cataract surgery but concluded
6
that a considerable proportion of these cases reflected the natural disease course or systemic
7
factors, rather than the influence of surgery.16
8 9
The presence of and management of DME can also impact cataract surgery decisionmaking. In the RISE/RIDE study, DME patients treated with ranibizumab who underwent
10
cataract surgery had an increase of an average of two lines in BCVA from baseline. In addition,
11
BCVA continued to improve slightly on average for months after surgery, supporting against the
12
idea that cataract surgery may accelerate DR/DME progression in the context of treatment.
13
Improvements for patients in the sham group from surgery seemed to be neutralized by initial
14
losses in BCVA due to untreated DME, with a net return to baseline with a combination of sham
15
treatments and surgery.17 Conversely, outer retinal atrophy is an additional concern that could
16
limit visual acuity outcomes in cataract surgery. Once thought to be a result of microvascular
17
damage, new research shows the neurodegeneration may be present and responsible for visual
18
symptoms before the formation of microaneurysms.18
19
Given the discrepancies in the literature regarding visual outcomes after cataract surgery
20
in diabetic patients, this study aims to define the relationship between postoperative visual
21
outcomes and pre-operative DR stage and presence of abnormal retinal thickness. Understanding
22
these patterns will help optimize future strategies for the management of cataracts in patients
23
with diabetes.
1
Methods
2
Study Design
3
A comprehensive retrospective chart review was performed for diabetic eyes undergoing
4
cataract surgery at Cole Eye Institute between September 2012 to September 2018. The study
5
obtained approval from the Cleveland Clinic Institutional Review Board (IRB) and all study
6
related procedures were performed in accordance with the Health Insurance Portability and
7
Accountability Act.
8
Included patients were 18 years or older, had a documented diagnosis of type 1 or 2
9
diabetes, and underwent phacoemulsification cataract surgery. Diabetic eyes were identified by
10
filtering patients with International Classification of Diseases (ICD) 9 and 10 codes for diabetes
11
mellitus and cross-referenced with patients who had received biometry in anticipation of cataract
12
surgery. If patients had surgery on both eyes, the eye that was operated on first was chosen for
13
analysis. Eyes were excluded based on the presence of other vitreoretinal or macular disease that
14
could influence cataract surgery outcome. Patients were also excluded if they missed
15
postsurgical follow-up at either 1 or 12 months or if they had received anti-VEGF (AVF) therapy
16
within the month prior to surgery.
17
Our primary objective was to determine change in VA as measured by Early Treatment
18
Diabetic Retinopathy Study (EDTRS) letters in diabetic eyes categorized by their preoperative
19
level of DR. Diabetic eyes were classified based on their pre-operative clinical diagnostic code in
20
the chart into groups: No DR, Mild/Moderate NPDR, Severe NPDR, and PDR. Pre-operative and
21
postoperative visual outcome data were collected at the pre-operative office visit and at 1- and
22
12-month visits following surgery. Retinopathy severity at the 12-month visit was determined
23
again from clinical diagnostic codes from the chart. Baseline characteristics gathered included
1
age, race, gender, laterality, and insulin dependence at the time of surgery. Lab values recorded
2
included HbA1c, creatinine, blood urea nitrogen, and estimated glomerular filtration rate within
3
3 months of surgery, which were excluded if taken due to acute hospitalization or ED visit. Our
4
secondary objective was to determine change in VA in ETDRS letters following cataract surgery
5
compared to pre-operative retinal thickness on optical coherence tomography (OCT). Patients
6
were divided in quartiles according to Central Subfield Thickness (CST) values on pre-operative
7
OCT, and outcome data was compared between quartiles. The presence of disorganization of the
8
retinal inner layers (DRIL) was evaluated on OCT at each of the time points. We defined DRIL
9
as the loss of distinction on OCT between the ganglion cell-inner plexiform layer complex, inner
10
nuclear layer, or outer plexiform layer independent of other retinal pathology, including macular
11
edema. Single, unmasked graders examined HD 5-line raster images through the macula to make
12
a subjective determination of the presence of DRIL.
13 14 15
Statistical Analysis Statistical analysis was done in SAS software (version 9.4; Cary, NC). Continuous
16
measures were summarized with Median [Q1, Q3], and categorical variables were summarized
17
with frequency (%). Baseline Retinopathy Extent (BRE) is analyzed as an ordered variable.
18
Relationships between continuous measures and BRE are quantified using Spearman’s rank
19
correlation coefficients (Spearman’s rho), and the Mantel-Haenszel test is used as a formal
20
hypothesis test of independence between two variables. Spearman’s rho ranges from -1 to 1,
21
where values closer to 1 (or -1, for a negative relationship) indicate very strong relationships, and
22
values closer to 0 indicate very weak relationships. Relationships between categorical variables
23
(DME (CST>320), Gender, Race, and Insulin Dependence) and BRE are analyzed with Kruskal-
1
Wallis Tests. Linear regression models are used to model change in visual acuity from baseline
2
to 1 month and baseline to 12 months. Outcomes were measured as improvement/change to
3
combat ceiling effect. P-values < 0.05 are considered significant, and are bolded.
1
Results
2 3 4
Patient demographics and baseline characteristics There were 138 eyes with No DR, 125 eyes with Mild/Moderate NPDR, 20 eyes with
5
Severe NPDR, and 72 eyes with PDR included in the analysis. Baseline characteristics and
6
change in VA and macular edema (ME) are presented in Table 1 by Baseline Retinopathy Extent
7
(BRE). Overall, 165 (46.5%) were male, the median age at surgery was 70.0 [(Q1, Q3); (64.0,
8
76.0)] years, median length of disease at surgery was 17.7 (10.4, 25.2) years, and median HbA1c
9
was 7.3 (6.5, 8.6)%. 208 (58.6%) of patients identified as White, 48 (13.5%) as Black, 2 (0.6%)
10
as Asian, 2 (0.6%) as American Indian/Alaska Native, 6 (1.7%) as Multiracial, and 15 (4.2%)
11
patients declined or had unavailable ethnicity data. Of the 124 eyes with OCT, median baseline
12
CST was 256 (231.5, 290.5) µm and 17 (13.7%) had ME.
13
There were significant differences when comparing visual acuity at 1 or 12 months to
14
baseline. A year after surgery, eyes without DR gained a median of 11.0 [(Q1, Q3), (5.0, 20.0)]
15
ETDRS letters from 65.0 (58.0, 70.0) before surgery, eyes with mild/moderate DR gained 10.0
16
(5.0, 22.0) from 65.0 (58.0, 76.0), eyes with severe NPDR gained 20.5 (8.0, 28.5) from 55.0
17
(26.0, 65.0), and eyes with PDR gained 15.0 (6.0, 29.5) from 55.0 (35.0, 61.0). Figure 1 shows
18
the development of visual acuities over time in a box plot. All groups improved significantly
19
from baseline to both 1 and 12 months, but there was loss of significance between 1 month and
20
12 months for eyes with Severe NPDR or PDR (Table 2). The variables that were significantly
21
associated with BRE included ETDRS at all time points (p<0.001), VA change at 1 month
22
following surgery (p=0.0261), age (p<0.001), race (p<0.001), length of disease (p<0.001), and
23
indicators of kidney function [BUN (p<0.02), Creatinine (p<0.001), eGFR (p<0.011)] (Table 1).
1
Of these, the strongest relationship was with length of disease, where there was a moderate
2
relationship with BRE (ρ=0.431) indicating worse DR with longer disease. Age has a weak
3
negative relationship with BRE (ρ= -0.358), where eyes of younger patients had worse DR at
4
presentation. Baseline CST or ME, gender, and VA change at 12 months were not significantly
5
associated with BRE.
6
In terms of progression, 9 (6.5%) eyes with No DR, 3 (2.4%) eyes with Mild/Moderate
7
NPDR, and 5 (4.0%) eyes with Severe NPDR showed progression of diabetic retinopathy at 12
8
months. Only 1 (0.7%) of eyes with No DR at baseline ended up receiving injection with anti-
9
VEGF agents over the year due to progression and development of ME; otherwise, 8 (6.4%) of
10
Mild/Moderate NPDR eyes, 10 (50.0%) of Severe NPDR eyes, and 12 (16.7%) of PDR eyes
11
received injections. 0 (0%) of No DR eyes, 10 (17.2%) of Mild/Moderate NPDR eyes, 2 (16.7%)
12
of Severe NPDR eyes, and 5 (14.7%) of PDR eyes had macular edema on OCT at baseline. 0
13
(0%) No DR eyes, 9 (39.1%) Mild/Moderate NPDR eyes, 7 (53.8%) Severe NPDR eyes, and 7
14
(26.9%) PDR eyes had macular edema on OCT at post-operative month 1. 2 (25%) No DR eyes,
15
8 (22.2%) Mild/Moderate NPDR eye, 6 (46.2%), Severe NPDR eyes, and 11 (27.5%) PDR eyes
16
had macular edema on OCT at 12 months. 10 (19.6%) of eyes with non-insulin dependent
17
diabetes mellitus (NIDDM) had disorganization of the inner retinal layers (DRIL) compared to
18
23 (31.5%) of eyes with insulin dependent diabetes mellitus at baseline. At 1 month, 6 (33.3%)
19
of NIDDM eyes had subjective signs of DRIL as compared to 24 (49.0%) of IDDM eyes on
20
OCT. At 12 months, 10 (33.3%) of NIDDM eyes had subjective signs of DRIL as compared to
21
33 (49.3%) of IDDM eyes on OCT.
22 23
Linear regression models for change in visual acuity
1
Baseline variables that were significantly associated with degree of vision recovered
2
following cataract surgery included age, BRE, and EDTRS (Table 3). For every additional year
3
older an eye is at surgery, VA change from baseline to POM 12 decreased by 0.20 letters for that
4
eye (p=0.008). BRE was also a significant driver of VA change post-surgery. At 12 months, eyes
5
with Mild/Moderate NPDR had worse VA change than eyes with No DR by 10.55±9.41 letters
6
(p=0.028); this number increased to 31.35±13.68 (p<0.001) and 30.82±9.60 (p<0.001) for Severe
7
NPDR and PDR eyes respectively.
8 9
Baseline ETDRS and its interaction with BRE indicated that the effect of baseline ETDRS was different for each level of BRE. For patients with No DR, each additional letter of
10
worse ETDRS at baseline resulted in a 0.88 letter VA improvement at POM 12. For
11
Mild/Moderate NPDR eyes, every additional letter of worse ETDRS at baseline resulted in a
12
0.13 diminished letter change compared to the No DR group (p=0.07), and an overall 0.75 letter
13
VA improvement at POM 12. For Severe NPDR eyes, every additional letter of worse baseline
14
ETDRS resulted in a 0.46 diminished letter change compared to the No DR group (p<0.001), and
15
an overall 0.42 letter VA improvement. For PDR eyes, every additional letter of worse baseline
16
ETDRS results in a 0.37 diminished letter change compared to No DR (p<0.001) and an overall
17
0.45 letter VA improvement. These result estimates are shown in Figure 2.
18
While HbA1c, BUN, creatinine, and eGFR were associated with baseline DR severity,
19
they were not independently associated with changes in visual outcome following cataract
20
surgery (Table 3). Table 4 illustrates linear regression results for eyes that had pre-operative
21
OCTs (n=124). Upon preliminary inspection of the CST distribution, it was found that the
22
relationship with VA change was not linear, and CST was thus broken up into quartiles. Eyes
23
with baseline CST between 257 and 289 µm see a higher VA improvement POM 1 than eyes
1
with CST below 231.5 µm by about 7.75 letters. Baseline CST is not a significant driver of VA
2
at POM 12.
3
Using the results, nomograms were constructed from our models to attempt to predict
4
outcomes of cataract surgery in diabetic patients. One such nomogram in Figure 3 includes a
5
demonstration of how to use this tool to predict visual acuity outcome in a particular patient.
6 7 8 9 10
Surgical complication rate Three eyes had complications at the time of cataract surgery. One eye without retinopathy had posterior capsular rupture and suprachoroidal hemorrhage during surgery. The eye ended up with visual acuity 20/200 at one year from baseline 20/60.
11
Another eye with PDR had visually significant retained cortical material that was
12
removed in a subsequent surgery without incident with a final visual acuity of 20/30. Finally, an
13
eye with PDR developed a posterior capsular rupture and vitreous hemorrhage later managed
14
with retinal surgery and had a visual acuity of 20/60.
15
1 2
Discussion Our study characterized the outcomes of cataract surgery in diabetic patients, stratifying
3
them by retinopathy stage, and examining baseline clinical and OCT characteristics to help
4
predict visual improvement. We found that regardless of BRE, patients had a significant gain in
5
visual acuity at POM 12 although these gains were greater for patients without DR or with
6
mild/moderate NPDR as compared to severe NPDR and PDR patients. We found that the visual
7
acuity gains at POM 12 was associated with age, baseline vision and retinopathy stage but not
8
associated with gender, race, insulin dependence, HbA1c, or renal function. The presence of
9
abnormal macular thickness preoperatively was overall not significantly predictive of visual
10
outcomes. We found some progression of diabetic retinopathy in our patient population but not
11
as much as other studies. Our study is the first, as far as we can tell, to attempt to estimate
12
improvement accounting for baseline characteristics, especially baseline visual acuity and
13
retinopathy severity, in a diabetic patient population.
14
We found that baseline visual acuity is a strong predictor of visual acuity gain, which is
15
in line with prior studies. Chew et. al. observed that a pre-operative VA worse than 20/100 had
16
an odds ratio of 8.7 of being unable to achieve a VA of 20/100, while being worse than 20/400
17
had a 12.6 odds ratio, but these were not stratified by retinopathy severity.19 Liu et. al. also
18
described a modest correlation of preoperative VA, diabetes, and diabetic retinopathy in general
19
with a lower probability of achieving a VA greater than 20/25.12 In our study, lower visual
20
acuities were correlated with visual acuity gains, with eyes with more severe retinopathy gaining
21
the most. This may be due to the fact that eyes with Severe NPDR or PDR presented with lower
22
baseline visual acuity, and therefore had more potential for improvement. This is not
23
incompatible with the studies mentioned above, as we can see from our data that VA gain is
1
additionally limited by BRE when outcomes are controlled for baseline VA. Reduced returns of
2
VA gain at lower baseline ETDRS were especially true for these eyes with Severe NPDR and
3
PDR in our study, even when accounting for ceiling effect of patients improving to 20/20 vision,
4
indicating that retina pathology may limit improvement. Nevertheless, the degree of
5
improvement of most eyes with this severity seem to suggest these eyes tended to have worse
6
cataract, and may have had surgery delayed due to providers’ unfavorable expectations of
7
improvement or to prioritize optimizing systemic and/or ocular disease. These patients may also
8
have presented for ophthalmic care with more mature cataracts than other patients. For example,
9
these patients may have more severe renal involvement in their diabetes that may complicate
10 11
scheduling surgery.20 Indeed, all groups showed significant improvement with cataract extraction despite level
12
of BRE, indicating the net positive impact of surgery, which has been demonstrated in multiple
13
studies showing improvement in the vast majority of patients.10,12,21–23 This is consistent with the
14
fact that VA before surgery is a cumulative representation of pathology of the visual axis,
15
including the lens and the retina. In addition, PDR eyes seemed to fare better than eyes with
16
Severe NPDR a year after surgery. This could be due to higher prevalence of prior treatment
17
with PRP in this group with better control of retinal disease before cataract surgery. Chew et. al.
18
showed as much of a 15% increase in probability of gaining more than 2 lines from surgery
19
compared to eyes that deferred PRP in a study of 270 eyes with more severe retinopathy.19
20
Quiescent disease could also explain why the PDR group had prevalence of ME closer to the
21
Mild/Moderate NPDR group during the follow-up period. Considering this, it seems that eyes
22
with appropriate management of retinopathy and undergoing cataract surgery have a favorable
23
prognosis despite retinopathy severity.
1
Eyes with more severe retinopathy who underwent cataract surgery were also younger. as
2
potentially uncontrolled blood sugars can precipitate cataract formation.4 Despite this, being
3
older also negatively affected the outcome of cataract surgery, consistent with previous literature
4
stating worst outcomes in older patients with no ocular comorbities.24 Eyes with severe
5
retinopathy were much more likely to belong to black patients, reflecting a disparity of disease
6
control in this population compared to non-Hispanic whites, but race by itself did not affect
7
visual acuity outcomes.25 Length of disease, insulin dependence, HbA1c, and
8
BUN/Creatinine/eGFR, while significantly worse overall with increasing DR, did not show a
9
completely linear relationship and did not correlate well with visual acuity outcomes. The
10
increased length of disease duration in patients with Mild/Moderate NPDR may reflect tendency
11
for better glycemic control in this patient population. Alternatively, this may be due to patients
12
with Severe NPDR being diagnosed by symptomatic manifestations including vision loss, rather
13
than diagnosed on screening tests, but this group was limited in power. Eyes with PDR tended to
14
present disproportionately later in the disease course and often were quiescent with some degree
15
of PRP before cataract surgery. Laboratory markers like HbA1c, BUN, Creatinine, and eGFR are
16
known fluctuate depending on factors like recent sugar control and hydration status, which could
17
affect their value in predicting visual acuity outcomes. Lower HbA1c values in the Severe NPDR
18
group could also be explained by the more severe renal impairment in this group, as lower eGFR
19
is associated with higher blood insulin levels.26
20
Rate of progression of retinopathy after surgery in our study was lower than in other
21
studies, with the Severe NPDR group having the highest rate of progression at 15%. Many
22
smaller studies have found high rates of progression compared to fellow non-operative
23
eyes.5,9,14,27 However, Wagner et. al. found that only 18.4% of eyes progressed compared to
1
14.3% of non-operative eyes in the first six months in a study of 223 patients, and this difference
2
ultimately disappeared after a period of observation.21 As Parness et. al. observed that 84% of
3
progression occurs in the first 6 months after surgery, this may be a transient worsening that
4
ultimately falls in line with the fellow eye.13 It may also reflect improved visualization of the
5
fundus on exam after cataract surgery. Another large study by Chew et. al. interpreted this
6
difference in progression as of borderline significance (p=0.03).19 The largest study by Jeng et.
7
al. observed a hazard ration of 1.48 for developing background DR but no difference in
8
progressing to PDR.6 Some studies postulated that HbA1c could predict progression, like Hong
9
et. al. who found that patients who progressed had higher average HbA1c of 8.0% vs. the 7.0%
10
of those who did not in their study of 169 patients.5 Parness et. al. similarly found less
11
progression in patients with an HbA1c of 7.5%, and Henricsson et. al. in their study of 70
12
eyes.13,22 However, Kato et. al. did not find such association, albeit in a smaller study of 66
13
patients.16 While our overall low rates of progression could therefore be explained by the lower
14
HbA1c values in our patient population, our Severe NPDR group progressed the most but had
15
lower HbA1c values than our other retinopathy groups. Maculopathy may be an important
16
predictor of progression as well, as Chiu et. al. found in their study of 107 operative eyes that
17
50% of these eyes progressed in DR severity.9
18
We observed higher rates of macular edema both at 1 month (as expected in
19
pseudophakic edema) and higher rates of persistent or recurrent macular edema at 12 months in
20
eyes with worse retinopathy, especially in eyes with Severe NPDR. Unlike progression of
21
retinopathy, our rates of macular edema agreed more with smaller studies done on the subject,
22
but our observations were only based on patients who received OCT at their follow-up visits. For
23
example, Parness et. al. found that 50% of their operative eyes developed DME, Krepler found
1
31% development compared to 13.5% in non-operative eyes in a study of 50 patients, and
2
Pollack found a rate of 39% in their 33 eyes.10,13,27 The largest of these studies by Chu et. al. of
3
over 81,984 patients found an 1.80 relative risk of developing post-operative macular edema
4
within 90 days of surgery in diabetics in general.7 However, they also observed much higher
5
rates of edema with other ocular comorbidities like capsular rupture, epiretinal membrane,
6
uveitis, retinal vein occlusion, and retinal detachment repair, some of which share risk factors
7
with diabetes. While many of these studies reflected pseudophakic macular edema worsened by
8
diabetes, Kutschan et. al. used a longer follow-up period to determine that rates of likely DME
9
were ultimately 6.8% at 19 months and persistent at 6.7% at 38 months, which were likely not
10
reflective of cataract surgery.15 Chu et. al. supported these findings as well, observing no long
11
term persistence of macular edema in operative vs. non-operative eyes.19
12
We used these findings to help prognosticate the amount of vision recovered in eyes with
13
cataract and diabetic retinopathy as their principle pathologies. As mentioned above, studies
14
prior often used thresholds of visual acuity to prognosticate vision, which could run the risk of
15
under or over-estimating the visual prognosis of patients who are subsequently categorized. The
16
nomogram built from the models included in this study could aid in clinical decision making of
17
when it would be beneficial for patients to have cataract surgery and setting realistic visual
18
expectations post-operatively. For example, it could be used to determine if surgery may
19
improve vision enough to allow a patient to drive according to the laws of their state.
20
This study had several limitations. Surgeons generally chose the eye with worse visual
21
acuity or more significant cataract to undergo phacoemulsification first, which often selected for
22
eyes with more guarded prognosis, or alternatively, more visual gain potential. Regardless, there
23
is selection bias as these were patients who were already clinically assessed as good surgical
1
candidates. For instance, they might not reflect all patients with diabetic retinopathy and
2
cataracts, including patients with diabetic complications such as tractional retinal detachments or
3
severe diabetic macular edema. There was therefore a relatively small sample of eyes with more
4
advanced DR, including Severe NPDR and PDR. The retrospective nature of this study limited
5
these numbers but the relatively low numbers of more advanced DR may also reflect some bias
6
in who was referred for cataract surgery. We measured lower rates of progression compared to
7
other studies but did not have fundus photographs on record to compare severe pre-operatively
8
vs. 12 months post-operatively, as some studies did.5 Additionally, a minority of eyes with OCT
9
at baseline had macular edema, which greatly limited our analysis, and subsequent OCTs were
10
not consistently done in the same patients. There may have been significant selection bias in
11
included OCTs as these tests were more frequently done in patients who had clinical findings
12
suspicious for macular edema. Patients with known DME may also have been less likely to be
13
referred for cataract surgery given concern of cataract surgery worsening the edema and concern
14
for visual potential. Our determination of DRIL was also not as rigorous as other studies which
15
used multiple, masked graders, and which attempted to quantify DRIL using micron
16
measurements or by dividing the central 1mm scan into multiple zones.28,29 We also excluded
17
patients who had intravitreal injections within the month prior to cataract surgery—those with
18
clinical diabetic macular edema who were receiving treatment would have been more likely to be
19
excluded given this.
20
Additionally, many of our patients were missing pre-operative laboratory data, and often
21
these tests were not collected for the purpose of pre-operative evaluation. This may have limited
22
the power of associating these factors to visual acuity outcomes. These factors do not seem to
23
have prognostic value on the surgery itself, which can be explained by the short time frames for
1
which these values had clinical utility. Given the safety of routine cataract surgery and lack of
2
need for general anesthesia, many of these tests have since been excluded from pre-operative
3
assessment.30
4
Cataract surgery could also lend itself to other complications for eyes with more severe
5
DR. While complications like vitreous hemorrhage, tractional retinal detachment, and post-
6
operative macular edema are generally treatable with surgery or intravitreal and topical therapies,
7
damage to the retina is generally irreversible.31 While our study saw immediate complications in
8
only 3 patients, we did not track the development of other complications over the course of the
9
first post-operative year.
10
In conclusion, cataract surgery is beneficial in the majority of patients with diabetic
11
retinopathy without severe concurrent macular pathology. However, visual acuity before surgery
12
and the severity of diabetic retinopathy can limit desired operative outcomes. Clinical judgment
13
of risks and benefits in cataract surgery is therefore complicated by diabetic disease and warrants
14
further consideration of outcomes. Further studies are needed to be understand how other
15
baseline clinical and imaging characteristics can help shape visual outcomes after cataract
16
surgery.
17
1
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1
Figure 1. Visual acuity in diabetic patients undergoing cataract surgery
2 3 4
Figure 2. Visual Acuity gain estimates per Baseline Retinopathy Extent group according to Table 3
5
1
Figure 3. Nomogram Modeling Change in Visual Acuity, Baseline to 12 Months
2 3 4 5 6
Characteristics of the patient eye can be added to the nomogram to predict visual acuity gain at 12 months. For example, a 60 year old non-insulin dependent male patient with an eye with mild/moderate non-proliferative diabetic retinopathy and a baseline visual acuity of 55 letters would be expected to gain 23 letters of visual acuity after surgery.
Table 1. Data according to Baseline Retinopathy Extent
Factor
None (N=138)
Mild/ Moderate NPDR (N=125)
Severe NPDR (N=20)
PDR (N=72)
Spearman pCorrelation value
Baseline CST*, Median µm [Q1, Q3] 240.5[230.0,256.0] 263.5[236.0,300.0] 273.5[223.0,301.5] 257.5[228.0,309.0] 0.089 0.326d Baseline ME (CST>320)*, No. (%) 0/20(0%) 10/58(17.2%) 2/12(16.7%) 5/34(14.7%) 0.275b ME at 1 month, No. (%) 0/5(0%) 9/23(39.1%) 7/13(53.8%) 7/26(26.9%) 0.133b ME at 12 months, No. (%) 2/8(25%) 8/36(22.2%) 6/13(46.2%) 11/40(27.5%) 0.433b ETDRS Baseline, Median letters [Q1, Q3] 65.0[58.0,70.0] 65.0[58.0,76.0] 55.0[26.0,65.0] 55.0[35.0,61.0] -0.287 <0.001d ETDRS 1 month, Median letters [Q1, Q3] 76.0[70.0,80.0] 76.0[70.0,80.0] 73.0[56.5,80.0] 70.0[56.5,76.0] -0.243 <0.001d ETDRS 12 months, Median letters [Q1, Q3] 80.0[76.0,85.0] 80.0[70.0,85.0] 70.0[63.0,80.0] 70.0[61.0,80.0] -0.304 <0.001d VA Change 1 month, Median letters [Q1, Q3] 10.0[4.0,15.0] 10.0[0.00,20.0] 15.0[3.0,41.5] 15.0[5.5,26.0] 0.118 0.0261d VA Change 12 months, Median letters [Q1, Q3] 11.0[5.0,20.0] 10.0[5.0,22.0] 20.5[8.0,28.5] 15.0[6.0,29.5] 0.090 0.091d Age, Median years [Q1, Q3] 72.0[67.0,79.0] 70.0[65.0,77.0] 69.5[63.0,73.0] 62.5[56.0,68.5] -0.358 <0.001d Gender, No. (%) 0.311b Male 56(40.6) 62(49.6) 9(45.0) 38(52.8) Female 82(59.4) 63(50.4) 11(55.0) 34(47.2) Race, No. (%) <0.001b White 104(75.4) 93(74.4) 1(5.0) 10(13.9) Black 34(24.6) 32(25.6) 19(95.0) 62(86.1) Length of Disease*, Median years [Q1, Q3] 8.4[4.2,16.4] 17.5[11.6,22.2] 13.8[4.2,23.2] 24.6[19.5,40.2] 0.431 <0.001d Insulin Dependence, No. (%) 37(26.8) 71(56.8) 11(55.0) 57(79.2) <0.001b HbA1c (within 3 mo. of surgery)*, Median % [Q1, Q3] 6.9[6.3,8.0] 7.6[6.8,9.0] 7.0[6.1,9.3] 7.7[6.9,8.9] 0.210 0.002d BUN*, Median mg/dL [Q1, Q3] 17.0[13.0,23.0] 18.5[15.0,23.0] 33.0[25.0,54.0] 19.0[16.0,27.0] 0.209 0.002d Creatinine*, Median mg/dL [Q1, Q3] 0.98[0.79,1.2] 0.98[0.81,1.3] 1.8[1.2,3.3] 1.2[0.84,1.7] 0.236 <0.001d eGFR*, Median mL/min [Q1, Q3] 60.0[57.0,60.0] 60.0[54.0,60.0] 38.0[15.0,60.0] 60.0[42.0,60.0] -0.174 0.011d * Data not available for all subjects. Missing values: Baseline CST = 231, Length of Disease = 285, HbA1c (within 3 mo. of surgery) = 141, BUN = 138, Creatinine = 136, eGFR = 140. p-values: b=Kruskal-Wallis test, c=Pearson's chi-square test, d=Mantel-Haenszel Trend test. CST = Central Subfield Thickness, ME = Macular Edema, ETDRS = Early Treatment of Diabetic Retinopathy Study, VA = Visual Acuity, BUN = Blood Urea Nitrogen, eGFR = estimated Glomerular Filtration Rate, NPDR = Non-Proliferative Diabetic Retinopathy, PDR = Proliferative Diabetic Retinopathy, CI = Confidence Interval.
Table 2. Difference in ETDRS Letters in Visual Acuity between visits by Baseline Retinopathy Extent Baseline to 1 month Baseline to 12 months Estimates 95% CI p-value Estimates 95% CI No DR 13.2 (10.0-16.4) 16.4 (13.3-19.6) <0.0001 Mild/Moderate NPDR 12.6 (9.4-16.5) 16.0 (12.8-19.3) <0.0001 Severe NPDR 20.6 (10.2-31.0) 21.5 (12.8-30.2) 0.0027 PDR 17.3 (13.3-21.3) 19.0 (14.0-23.9) <0.0001
p-value <0.0001 <0.0001 0.0008 <0.0001
Estimates 3.2 3.1 0.9 1.7
1 to 12 months 95% CI (1.9-4.5) (1.5-4.7) (-6.0-7.8) (-2.4-5.8)
p-value 0.0004 0.0064 0.8273 0.2867
Table 3. Regression Results: Modeling Change in VA Condition Intercept Age (years) Gender: Female (vs Male) Race: Black (vs White) Baseline ETDRS (letters) Insulin Dependence: Yes (vs No) Baseline Retinopathy Extent: Mild/Moderate NPDR (vs None) Severe NPDR (vs None) PDR (vs None) Baseline ETDRS*Baseline Retinopathy Extent Mild/Moderate NPDR (vs None) Severe NPDR (vs None) PDR (vs None) HbA1c (%) BUN (mg/dL) Creatinine (mg/dL) eGFR (mL/min)
Baseline to 1 Month Estimates 95% CI 80.43 67.74 93.11 -0.2 -0.35 -0.05 -1.38 -3.88 1.13 1.55 -1.48 4.58 -0.84 -0.95 -0.73 -1.83 -4.55 0.89
p-value <0.001 0.009 0.282 0.314 <0.001 0.187
Baseline to 12 Months Estimates 95% CI 86.46 73.79 99.12 -0.2 -0.35 -0.05 -1.66 -4.16 0.85 -0.04 -3.06 2.99 -0.88 -0.99 -0.78 0.46 -2.25 3.18
p-value <0.001 0.008 0.194 0.982 <0.001 0.738
-4.09 -20.22 -29.19
-13.51 -33.93 -38.81
5.33 -6.5 -19.57
0.393 0.004 <0.001
-10.55 -31.35 -30.82
-19.96 -45.03 -40.42
-1.15 -17.66 -21.22
0.028 <0.001 <0.001
0.04 0.27 0.39 -0.97 -0.11 -0.6 -0.07
-0.1 0.02 0.23 -2.09 -0.38 -2.54 -0.29
0.19 0.53 0.56 0.15 0.15 1.34 0.16
0.57 0.038 <0.001 0.088 0.41 0.544 0.555
0.13 0.46 0.37 -0.68 0.23 0.71 0.05
-0.01 0.21 0.21 -1.76 -0.03 -1.16 -0.16
0.28 0.72 0.54 0.4 0.48 2.59 0.27
0.07 <0.001 <0.001 0.215 0.081 0.454 0.639
Table 4. Regression Results: Modeling Change in VA – OCT Group Baseline to 1 month Condition Estimates 95% CI Intercept 74.28 59.09 89.47 Baseline ETDRS (letters) -1.02 -1.26 -0.78 Baseline Retinopathy Extent: Mild/Moderate NPDR (vs None) -13.41 -32.94 6.13 Severe NPDR (vs None) -28.45 -50.23 -6.67 PDR (vs None) -40.61 -59.02 -22.2 Baseline CST Quartiles (µm) Q2 [232 to 256] (vs Q1, less than 231.5) 3.3 -2.79 9.39 Q3 [257 to 289] (vs Q1, less than 231.5) 7.75 1.83 13.67 Q4 [290 to 445] (vs Q1, less than 231.5) -0.51 -6.4 5.38 Baseline ETDRS*Baseline Retinopathy Extent Mild/Moderate NPDR (vs None) 0.18 -0.13 0.48 Severe NPDR (vs None) 0.41 0.03 0.8 PDR (vs None) 0.61 0.3 0.92
p-value <0.001 <0.001
Baseline to 12 months Estimates 95% CI p-value 79.67 65.95 93.4 <0.001 -1.06 -1.28 -0.85 <0.001
0.177 0.011 <0.001
-26.68 -53.97 -58.4
-44.32 -73.65 -75.03
-9.03 -34.29 -41.77
0.003 <0.001 <0.001
0.286 0.011 0.865
2.89 3.97 -0.79
-2.62 -1.38 -6.11
8.39 9.31 4.54
0.301 0.145 0.77
0.247 0.035 <0.001
0.4 0.85 0.94
0.12 0.5 0.66
0.67 1.2 1.22
0.005 <0.001 <0.001
Eyes with severe non-proliferative or proliferative diabetic retinopathy had less visual acuity improvement after cataract surgery compared to other diabetic eyes in a study of 355 cases, especially if they had worse preoperative visual acuity.