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Continuing Medical Education:
Influence of
diabetes and
diabetes type on
anatomic and visual
outcomes following
central rein vein
occlusion
JG Santiago, S Walia, JK Sun, JD Cavallerano,
ZA Haddad, LP Aiello and PS Silva
Release date: 14 February 2014; Expiration date: 14 February 2015
This activity has been planned and implemented in accordance with the Essential Areas and policies
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Medscape, LLC designates this Journal-based CME activity for a maximum of 1 AMA PRA Category 1
Credit(s)t. Physicians should claim only the credit commensurate with the extent of their
participation in the activity.
All other clinicians completing this activity will be issued a certificate of participation. To
participate in this journal CME activity: (1) review the learning objectives and author disclosures;
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Learning objectives
Upon completion of this activity, participants will be
able to:
1. Compare the prevalence of central retinal vein
occlusion (CRVO) in diabetic patients and nondia-
betic patients
2. Describe outcomes after CRVO in diabetic patients
and nondiabetic patients
3. Describe outcomes after CRVO in patients with
type 1 diabetes and those with type 2 diabetes
Authors/Editors disclosure information
Andrew Lotery has disclosed the following relevant financial
relationships: Served as an advisor or consultant for:
Allergan, Bayer, and Novartis,
Served as a speaker or a member of a speakers bureau
for: Novartis, Received grants for clinical research from:
Novartis
Juan G Santiago has disclosed no relevant financial
relationships.
Saloni Walia has disclosed no relevant financial relationships.
Jennifer K Sun has disclosed no relevant financial
relationships.
Jerry D Cavallerano has disclosed no relevant financial
relationships.
Zeina A Haddad has disclosed no relevant financial
relationships.
Lloyd Paul Aiello has disclosed the following relevant
financial relationships: Served as an advisor or consultant for
Merck, Genzyme, Vantia, KalVista, Thrombogenetics, and
Eisai; received travel expenses from Optos.
Paolo S Silva has disclosed the following relevant financial
relationships: Received grants for clinical research from
unrestricted grant funding to the Joslin Diabetes Center
from Optos plc.
Journal CME author disclosure information
Laurie Barclay has disclosed no relevant financial
relationships.
Eye (2014), 1–10
&2014 Macmillan Publishers Limited All rights reserved 0950-222X/14
www.nature.com/eye
Influence of
diabetes and
diabetes type on
anatomic and visual
outcomes following
central rein vein
occlusion
JG Santiago
1,3
, S Walia
1,3
, JK Sun
1,2
,
JD Cavallerano
1,2
, ZA Haddad
1
, LP Aiello
1,2
and PS Silva
1,2
Abstract
Purpose To determine the influence of
diabetes and diabetes type on ocular
outcomes following central retinal
vein occlusion (CRVO).
Methods Retrospective chart review of all
patients evaluated over a 4-year period in a
tertiary diabetes eye care center. Ophthalmic
findings were recorded including visual
acuity and the presence of retinal
neovascularization at presentation, after
3–6 months, and at last follow-up.
Results The records of 19 648 patients
(13 571 diabetic; 6077 nondiabetic) were
reviewed. The prevalence of CRVO in
diabetic patients (N¼72) and nondiabetic
patients (N¼27) were 0.5 and 0.4%,
respectively. Disc neovascularization
(21.3 vs 0.0%, P¼0.05) and panretinal
photocoagulation (PRP) (48.7 vs 21.4%,
P¼0.01) were more common in diabetic
patients compared with nondiabetic patients.
Compared with type 2 diabetic patients,
retinal neovascularization (28.6 vs 3.7%,
P¼0.004) and subsequent PRP (78.6 vs 41.9%,
P¼0.01) were more likely in type 1 patients.
Optic nerve head collateral vessels (CVs)
were observed less than half as often (21.4 vs
56.5%, P¼0.04) in patients with type 1
diabetes. Presence of optic nerve head
CVs at baseline was associated with less
likelihood of PRP (14.3 vs 46.1%, P¼0.03).
Conclusions In this cohort, the rates of
CRVO in diabetic and nondiabetic patients
were similar to previously published
population-based studies. Following CRVO,
diabetic patients had higher rates of disc
neovascularization and were more likely to
require subsequent PRP than nondiabetic
patients. As compared with CRVO patients
with type 2 diabetes, patients with type 1
diabetes and CRVO had worse anatomic
outcomes with substantially increased risks
of retinal neovascularization and PRP;
however, final visual acuity outcomes
were similar.
Eye advance online publication, 14 February
2014; doi:10.1038/eye.2014.1
Keywords: central retinal vein occlusion;
diabetes mellitus; retinal neovascularization;
retinal ischemia; panretinal laser
photocoagulation
Introduction
Central retinal vein occlusion (CRVO) is a
retinal vascular disease that frequently results
in significant visual loss.1–3 Population-based
studies estimate that the prevalence ranges from
0.1%4to 0.8%5and that the 15-year cumulative
incidence is 0.5%.6CRVO is observed in all
age groups, with increasing incidence with
advancing age.6,7 CRVO is classified into two
distinct groups with different visual outcomes:
nonischemic and ischemic.8The ischemic CRVO
generally presents with poorer visual acuity at
baseline, worse visual prognosis and higher risk
of developing neovascularization as compared
with the nonischemic group.8,9 Visual decline in
patients with CRVO may occur from ischemic
injury to the retina, macular edema, vitreous
hemorrhage, retinal neovascularization, and/or
1
Beetham Eye Institute,
Joslin Diabetes Center,
Boston, MA, USA
2
Department of
Ophthalmology, Harvard
Medical School, Boston,
MA, USA
Correspondence:
PS Silva, Beetham Eye
Institute, Joslin Diabetes
Center, 1 Joslin Place,
Boston, MA 02215, USA
Tel: +1 617 309 2554;
Fax: +1 617 309 2545.
E-mail: paoloantonio.silva@
joslin.harvard.edu
3
These authors contributed
equally to this work.
Received: 5 June 2013
Accepted in revised form:
21 October 2013
CLINICAL STUDY
Influence of diabetes and diabetes type on CRVO
JG Santiago et al
2
neovascular glaucoma.10 There is an associated
vision-related decline in quality of life.11
Multiple systemic and ocular conditions are associated
with CRVO.7,12–21 Many studies have confirmed higher
prevalence of diabetes mellitus (DM) in patients with
CRVO.16,21–24 Co-existing DM is reported in 10–34% of
patients with CRVO and may affect the natural history in
this subgroup of patients.25,26 Patients with DM have a
higher risk of subsequently developing ischemic CRVO
and neovascular complications.14,27 A higher prevalence
of DM has been noted among those patients developing
CRVO. However, detailed assessment of risk factors in
DM patients that may predict the development of retinal
ischemia and neovascularization following CRVO is
lacking. The influence of DM type on the natural course
of CRVO is also unknown. In the current study, we
compared nondiabetic and diabetic patients with CRVO
and evaluated the effect of diabetes type and systemic
and ocular risk factors on ophthalmic outcomes in an
academic tertiary care diabetes center.
Materials and methods
A structured, retrospective medical record review of all
patients seen at the Beetham Eye Institute of the Joslin
Diabetes Center from 1 January 2004 to 15 November
2008 was performed. The study was approved by the
Joslin Diabetes Center Institutional Review Board prior
to the review of the patients’ records. A structured
electronic search query from the electronic medical
record was used to identify all CRVO patients with
ICD-9 coded diagnosis of 362.35 (CRVO). The individual
medical records of all identified patients were retrieved
and all pertinent information was recorded on a
standardized form. The diagnoses of CRVO and DM
were confirmed based on the systemic and clinical
characteristics documented at the initial visit. Diabetes
type was determined based on the physician coded
ICD-9 diagnosis in the patient’s electronic medical
records.
Baseline demographic factors including age, gender,
ethnicity, and pertinent systemic medical risk factors
associated with progression of diabetic retinopathy (DR)
or increased risk of CRVO were noted at the initial visit.
The systemic medical and ophthalmic risk factors
evaluated included those published in previous studies:
hypertension, DM, hyperlipidemia, cardiovascular
disease, smoking history, open-angle glaucoma, and
elevated intraocular pressure (IOP).7,12–21 The
ophthalmic findings from all patients at the initial (visit
I), 4-month (visit M; window ¼3–6 months), and final
follow-up (visit F) were recorded. Data from the visit
prior to development of CRVO were also recorded when
available (visit P). If a patient was diagnosed with
bilateral CRVO, ophthalmic findings were recorded
individually for each eye at each of the three specified
visits.
Recorded visual and anatomic outcomes included
best-corrected Early Treatment Diabetic Retinopathy
Study (ETDRS) protocol visual acuity; IOP measured
by Goldman applanation tonometry; presence of
neovascularization of the iris and/or angle, optic disc,
or elsewhere on the retina; presence of neovascular
glaucoma; clinical DR severity; presence of macular
edema; and presence of optic nerve head collateral
vessels (CVs). All refractionists, visual acuity examiners,
and visual examination rooms were clinical trial certified.
Standardized templates were used to record the presence
of neovascularization, CV, DR severity, and macular
edema. Consistency of ophthalmologists’ grading of
DR at the Beetham Eye Institute has been established as
comparable to the inter-reader results of the ETDRS
study and masked evaluation of ETDRS standardized
photographs.28 Fundus photography and fluorescein
angiography were reviewed when the images were
available. Retinal ischemia was established based on
capillary nonperfusion observed on fluorescein
angiography. The dates of all ophthalmic procedures
after onset of CRVO were recorded, including those for
cataract surgery, glaucoma surgery, intravitreal injection,
panretinal laser photocoagulation, vitrectomy, and radial
optic neurotomy.
We certify that all applicable institutional and
governmental regulations were followed during this
research.
Statistical analysis
All analyses were performed using Statistical Analyses
System software V9.2 (SAS Institute, Cary, NC, USA).
For patients with fewer than three visits, the ‘last
observation carried forward’ method was used. If the last
visit (visit F) was within 3–6 months of baseline, data
from this visit were also used for analyses pertaining to
the visit M 3–6-month follow-up. Nonparametric
analyses (Wilcoxon rank sums) were used to compare
distributions of continuous variables between groups.
The w
2
-test was used to compare frequencies of
categorical variables. For these exploratory analyses,
Po0.05 was defined as statistically significant.
Results
A total of 104 eyes of 99 patients with CRVO were
identified from the 5-year cohort of 19648 patients. The
overall prevalence was 0.5%. The right eye only was
affected in 46 patients (44.2%) and 5 patients (5.1%)
had bilateral CRVO. Of the 13 571 DM patients, 76 eyes of
Influence of diabetes and diabetes type on CRVO
JG Santiago et al
3
Eye
72 patients developed CRVO (0.5%). Among the 6077
nondiabetic patients, 28 eyes of 27 patients developed
CRVO (0.4%). Individual eye involvement and bilateral
CRVO prevalence did not differ significantly between
DM and nondiabetic patients. The mean age for the
entire CRVO cohort was 65.3±14.2 (range: 30.1–95.1)
years. CRVO patients with DM tended to be younger
compared with CRVO patients without DM but this
difference was not statistically significant (63.9 vs 69.0
years, P¼0.22). The epidemiological characteristics
of the study population are presented in Table 1.
Comorbidities in diabetic vs nondiabetic CRVO patients
Among CRVO patients, the prevalence of systemic
hypertension, hyperlipidemia, and cardiovascular
disease was 78.8, 56.6 and 34.3%, respectively. Less
prevalent was the presence of anemia (9.1%) and renal
disease (7.1%). The prevalence of systemic hypertension
(84.7 vs 63.0%, P¼0.02), use of antihypertensive
medications (80.6 vs 51.9%, Po0.01), cardiovascular
disease (40.3 vs 18.5%, P¼0.04), hyperlipidemia
(66.7 vs 29.6%, Po0.001), and hyperlipidemia treatment
(61.1 vs 25.9%, P¼0.003) were significantly higher in
DM patients than in nondiabetic patients (Table 2).
In contrast, systolic and diastolic blood pressures (BPs)
were not significantly different in DM patients (mean BP:
136/75 mmHg) compared with nondiabetic patients
(mean BP: 131/75 mmHg). DM patients had a higher
prevalence of renal disease (9.7 vs 0.0%, P¼0.93), anemia
(9.7 vs 7.4%, P¼0.72), smoking history (23.6 vs 22.2%,
P¼0.80), and use of anticoagulation medications (41.7 vs
37.0%, P¼0.78) such as aspirin, clopidogrel, and/or
warfarin as compared with nondiabetic patients;
however, these differences were not statistically
significant.
DR was present at baseline exam in 66.7% of CRVO
eyes of DM patients. Among these eyes with DR, 64.6%
had mild nonproliferative DR (NPDR), 12.5% had
moderate–severe NPDR, and 22.9% had proliferative DR
(PDR). At the first visit following CRVO (3–6 months),
there was an increase in the percentage of patients with
PDR (from 15.3 to 23.9%) as well as moderate NPDR
(from 4.2 to 7.5%) and a decrease in the percentage of
patients with mild NPDR (from 43.1 to 28.4%).
Table 1 Baseline characteristics in diabetic vs nondiabetic
patients with CRVO
CRVO
with
DM
CRVO
without
DM
P-value
Total patients 72 27
Total eyes 76 28
Total bilateral CRVO 4 (5.6%) 1 (3.7%)
Eyes with angiograms 36 (47.4%) 18 (64.3%) 0.35
Ischemic CRVO 5 (13.9%) 1 (5.6%) 0.65
Mean age (years) 63.9 69.0 0.22
Gender 0.43
Male (%) 43.1 (n¼31) 51.9 (n¼14)
Female (%) 56.9 (n¼41) 48.1 (n¼13)
Ethnicity 0.17
Caucasian (%) 78.7 (n¼48) 82.3 (n¼14)
African-American (%) 14.7 (n¼9) 5.9 (n¼1)
Hispanic (%) 6.6 (n¼4) 5.9 (n¼1)
Asian (%) 0.0 (n¼0) 5.9 (n¼1)
Abbreviations: CRVO, central retinal vein occlusion; DM, diabetes mellitus.
Table 2 Prevalence of systemic risk factors at baseline visit in patients with CRVO
CRVO with DM CRVO without DM P-value
Systolic blood pressure, mean (±SD) (mmHg) 137 (±19) 131 (±14) 0.46
Diastolic blood pressure, mean (±SD) (mmHg) 75 (±12) 78 (±14) 0.37
Presence of hypertension (%) 84.7 63.0 0.02
Use of antihypertensive drugs (%) 80.6 51.9 0.008
Hyperlipidemia (%) 66.7 29.6 o0.001
Use of lipid lowering drugs (%) 61.1 25.9 0.003
CVD (%) 40.3 18.5 0.04
Use of anticoagulation drugs (%) 41.7 37.0 0.78
Aspirin (%) 31.9 25.9 0.63
Warfarin (%) 8.3 7.4 0.92
Clopidogrel (%) 8.3 3.7 0.45
Renal disease (%) 9.7 0.0 0.93
Anemia (%) 9.7 7.4 0.72
Smoking 0.95
Never (%) 72.2 77.8
Former (%) 16.7 14.8
Present (%) 6.9 7.4
Abbreviations: CRVO, central retinal vein occlusion; CVD, cardiovascular disease; DM, diabetes mellitus.
Influence of diabetes and diabetes type on CRVO
JG Santiago et al
4
Eye
CRVO outcomes in diabetic vs nondiabetic patients
In the subgroup of eyes with visits prior to the onset of
the CRVO (N¼88), the mean logMAR visual acuity was
0.17 (Snellen equivalent 20/30) prior to developing
CRVO. Mean visual acuity at the initial visit after CRVO
declined to 0.79 (Snellen equivalent 20/123) and the
mean logMAR at last follow-up was 1.16 (Snellen
equivalent 20/290). Patients with DM tended to have
slightly worse logMAR visual acuity at the initial visit
after CRVO (0.8316 vs 0.6653; P¼0.89) and final visit
(1.1771 vs 1.1206; P¼0.95); however, these differences
were not statistically significant.
Ophthalmic procedure frequencies are shown in
Table 3. Panretinal photocoagulation (PRP) after CRVO
was more than twice as common in eyes of patients with
DM (48.7%) than in eyes of patients without DM (21.4%,
P¼0.01). The presence of optic nerve head CVs at initial
visit was associated with more than threefold lower rates
of PRP (14.3 vs 46.1%, P¼0.03). Cataract extraction rates
were similar in CRVO eyes with DM compared with
CRVO eyes without DM (15.8 vs 10.7%, P¼0.20).
Similarly, there were no statistical differences noted for
intravitreal injection, pars plana vitrectomy, glaucoma
surgery, or radial optic neurotomy.
Ischemic vs nonischemic CRVO outcomes in diabetic and
nondiabetic patients
Fluorescein angiography was available and reviewed
according to Standard of Care vs Corticosteroid for
Retinal Vein Occlusion (SCORE) study criteria in 54 eyes
(52%). Baseline parameters of eyes with angiograms did
not differ significantly from eyes where angiograms were
not available. As shown in Table 1, 6 (11%) of the 54
evaluated eyes had ischemic CRVO by fluorescein
angiography, and 5 (83.3%) of these eyes were from
diabetic patients (1 eye type 1 DM, 4 eyes type 2 DM).
In this partial cohort, trends were evident, but none
reached statistical significance. Ischemic CRVO tended
to be more common in eyes of subjects with DM than
in those without DM (13.9 vs 5.6%, P¼0.36). Ischemic
CRVO tended to be slightly more common in eyes with
type 2 DM than in eyes with type 1 DM (15.4 vs 10%,
P¼0.68). However, owing to the small number of
ischemic CRVO in this cohort overall, comparisons of
risks for ischemic vs nonischemic CRVO could not
be analyzed.
CRVO and glaucoma
Primary open-angle glaucoma and use of glaucoma
medications were more common in nondiabetic patients.
Nondiabetic subjects with CRVO were over four times
more likely to be using glaucoma medications prior
to CRVO diagnosis (62.5 vs 13.2%, P¼0.002) and had
a lower mean IOP (14.0 vs 16.1 mmHg, P¼0.02) than
diabetic subjects who developed CRVO. All eyes
with diabetes and ischemic CRVO were on glaucoma
medications on follow-up (100 vs 26,9%, P¼0.03) and
on the final visit (100 vs 46.4%, P¼0.05).
CRVO outcomes by diabetes type
Among diabetes patients with CRVO, 19.4% (n¼14) had
type 1 DM and 80.6% (n¼58) had type 2 DM. The mean
duration of DM was 16.0±10.4 (1.5–45.0) years, with a
shorter duration observed among type 1 DM patients
(12.1±6.7 years) than for type 2 DM patients (27.1±10.0
years, Po0.0001). The mean HbA1c in DM patients was
7.7±1.3% (5.0–11.3). The mean HbA1c was higher in type
1 DM (8.4±1.2%) than in type 2 DM (7.6±1.2%, P¼0.02)
(Table 4).
Neovascularization of all types tended to be more
common in DM patients with CRVO than in nondiabetic
patients with CRVO. This finding was particularly true
for neovascularization of the disc (NVD) after CRVO,
which was much more likely in eyes of DM patients as
compared with nondiabetic patients (21.3 vs 0.0%,
P¼0.05, Table 5). Compared with type 2 DM, retinal
Table 3 Comparison of frequency of ophthalmic procedures in CRVO patients with and without diabetes and patients with type 1
and type 2 DM
Procedures CRVO with
DM (N¼76)
CRVO without
DM (N¼28)
P-value CRVO with type 1
DM (N¼14)
CRVO with type 2
DM (N¼62)
P-value
PRP 48.68% (37) 21.43% (6) 0.01 78.57% (11) 41.94% (26) 0.01
Intravitreal injection 9.21% (7) 10.71% (3) 0.82 7.14% (1) 9.68% (6) 0.77
Pars plana vitrectomy 13.16% (10) 7.14% (2) 0.39 14.29% (2) 12.90% (8) 0.89
Cataract surgery 15.79% (12) 10.71% (3) 0.20 14.29% (2) 17.74% (11) 0.76
Glaucoma surgery 3.95% (3) 0.00% (0) 0.29 0.00% (0) 4.84% (3) 0.40
Radial optic neurotomy 0.00% (0) 3.57% (1) 0.10 0.00% (0) 0.00% (0)
Abbreviations: CRVO, central retinal vein occlusion; DM, diabetes mellitus; N, Number of eyes with CRVO; PRP, panretinal photocoagulation.
Influence of diabetes and diabetes type on CRVO
JG Santiago et al
5
Eye
neovascularization from CRVO was eight times more
likely (28.6 vs 3.7%, P¼0.004) and optic nerve head CVs
were observed less than half as often (21.4 vs 56.5%,
P¼0.04) in patients with type 1 DM. CRVO patients with
type 1 DM were nearly twice as likely to undergo
subsequent PRP as compared with patients with type 2
DM (78.6 vs 41.9%, P¼0.01). However, visual outcomes
between type 1 and type 2 DM patients with CRVO were
not significantly different (initial visit, P¼0.11; follow-up
visit, P¼0.36; final visit, P¼0.68).
Discussion
DR and retinal vein occlusions are among the most
common vascular disorders affecting the retina.29 There
are many factors common to both these disorders: older
age, hypertension, hyperlipidemia, and coagulation
disorders. Both have similar treatment options including
PRP and intravitreal injections of vascular endothelial
growth factor inhibitors. Studies focusing on vitreous
factors mediating these disorders have shown increased
expression of similar proteins30,31 and it is likely
that both CRVO and DR share similar pathogenic
mechanisms in relation to the final pathways resulting
in retinal neovascularization.
Previously reported prevalence of CRVO overall
ranges from 0.1%4to 0.8%.5In the current study, the
prevalence of 0.5% is consistent with prior reports.
Although patients with CRVO have a higher prevalence
of DM than the general population,16,21–24 in the current
study the prevalence of CRVO in DM patients was 0.5%,
and was not statistically different than the prevalence of
0.4% observed in the nondiabetic patients. The similarity
between these two groups may reflect the academic
diabetes-specific tertiary care medical center referral
setting in which this study was conducted. Older age has
been associated with increasing prevalence of CRVO6,7 as
well as more ischemic CRVO in the general population.32
Potentially, diabetes itself does not increase the risk of
developing CRVO.33 In this study, there was no statistical
difference in the mean age of CRVO patients with DM
as compared with nondiabetic patients with CRVO.
However, patients with DM and CRVO were significantly
older compared with the overall cohort of DM patients
reviewed in the study, consistent with increasing age
being a risk factor for CRVO. Consistent with previous
studies,25,34 we observed that DM patients with CRVO
developed retinal neovascularization (particularly NVD)
more frequently than nondiabetic patients with CRVO.
Increased risk of neovascularization would be consistent
with the generally increased state of retinal ischemia in
the diabetic patient.
Interestingly, DM type had a substantial impact on
CRVO anatomic outcomes. There was more than an
eightfold increased risk of developing neovascularization
and a twofold greater rate of receiving PRP in type 1 DM
patients as compared with type 2 DM patients. This
finding is consistent with the generally greater risk of
neovascular complications observed in type 1 compared
with type 2 DM patients in population- and clinic-based
reports.35 Optic nerve head CVs were observed less than
half as often in patients with type 1 DM and the presence
of these CVs at baseline was associated with a more than
threefold reduction in PRP. However, visual outcomes
between type 1 and type 2 DM patients with CRVO were
not significantly different, likely as a result of the
effectiveness of current treatment regimens and limited
number of events in specific subgroups.
The role of retinochoroidal CVs on the natural history
of CRVO is unclear. Some studies report that the
development of CVs may be associated with a better
visual prognosis in patients with CRVO. However,
Hayreh et al suggested that CVs formation may be
associated with a delay in resolution of macular edema
and worse prognosis.9Recent data from the SCORE
study may indicate that the development of venous
collaterals does not demonstrate an independent
association with visual acuity in eyes with CRVO.36
Although limited to only 15 instances of CV formation,
our data did not demonstrate a significant difference in
the incidence of collateral formation following CRVO in
patients with or without DM.
Although the number of eyes identified in this study
that developed CRVO was relatively small (104 eyes of 99
patients), a total of 19 648 patients (13 571 with DM) were
evaluated over nearly a 5-year period. Thus, this study
represents one of the largest reports of DM patients with
CRVO (76 eyes) and one of the only studies to specifically
report on diabetes type. Comparatively, the Central Vein
Occlusion Study (CVOS), which established the
guidelines for panretinal laser photocoagulation in
Table 4 Baseline characteristics in type 1 vs type 2 diabetes
patients with CRVO
Type
1DM
Type 2
DM
P-value
Total Patients (%) 19.4 (n¼14) 80.6 (n¼58)
Duration of DM,
mean±SD (years)
27.1±10.0 12.1±6.7 o0.0001
HbA1c value,
mean±SD (%)
8.4±1.2 7.6±1.2 0.02
Main treatment
Lifestyle/diet (%) 6.9 (n¼4)
Oral hypoglycemic (%) 62.1 (n¼36)
Insulin (%) 100 (n¼14) 31.0 (n¼18)
Abbreviations: CRVO, central retinal vein occlusion; DM, diabetes
mellitus; HbA1c, hemoglobin A1c.
Influence of diabetes and diabetes type on CRVO
JG Santiago et al
6
Eye
patients with CRVO, enrolled only five patients with
diabetes in each study arm.27 The Beaver Dam
population-based study evaluated 4068 patients over a
15-year period and reported only 62 incident CRVO
cases.6The more recent SCORE study enrolled 62
diabetes CRVO patients.37 In none of these reports was
diabetes type specifically evaluated.
The retrospective nature of the current study is a
limitation; however, the drawbacks inherent in this study
design are mitigated in this particular case by evaluation
of the entire patient population over the period, use of
standardized diabetes-specific electronic medical record
with comprehensive diabetes and systemic history,
standardized refraction and visual acuity measurement,
study-certified data acquisition personnel, and uniform
retinopathy grading. Fluorescein angiograms were only
obtained in a subset of patients, which is a limitation of
the study; however, the baseline demographic did not
significantly differ in eyes that had an angiogram
performed at baseline as compared with eyes that did not
have an angiogram. Furthermore, the available
angiograms were evaluated based on SCORE study
criteria that was previously demonstrated to be a
reproducible assessment of retinal vascular leakage
severity and capillary nonperfusion.38
In conclusion, this study suggests not only that DM
increases the likelihood of retinal neovascularization and
the need for PRP in patients with CRVO, but also that
diabetes type is an important indicator of key ocular
outcomes. Patients with type 1 DM were at eightfold
higher risk for developing neovascularization following
CRVO as compared with patients with type 2 DM, and
twice as likely to receive PRP and half as likely to
develop optic nerve head CVs. These data suggest that
following CRVO, patients with type 1 DM should be
followed especially carefully for development of retinal
complications and need for treatment. However, given
current care approaches, visual acuity outcomes are
similar following CRVO for type 1 DM, type 2 DM, and
nondiabetic patients.
Table 5 Prevalence of neovascularization and retinochoroidal collateral formation in patients with CRVO.
CRVO eyes CRVO eyes with DM CRVO eyes without DM P-value
a
Any neovascularization 44.44% (32) 49.09% (27) 29.41% (5) 0.15
Rubeosis (NVI and/or NVA)
Any visit 28.99% 30.77% 23.53% 0.57
Baseline 3.85% 5.26% 0.00% 0.22
4-month follow-up 17.91% 20.00% 11.76% 0.44
Last visit 12.62% 13.33% 10.71% 0.72
Neovascularization of the disc
Any visit 16.13% 21.28% 0.00% 0.05
Baseline 4.85% 6.67% 0.00% 0.16
4-month follow-up 8.96% 12.00% 0.00% 0.13
Last visit 3.16% 4.41% 0.00% 0.27
Neovascularization elsewhere
Any visit 12.90% 14.89% 6.67% 0.41
Baseline 3.88% 5.33% 0.00% 0.21
4-month follow-up 2.99% 2.00% 5.88% 0.42
Last visit 3.16% 4.41% 0.00% 0.27
Neovascular glaucoma
Any visit 10.94% 12.77% 5.88% 0.44
Baseline 1.94% 2.67% 0.00% 0.38
4-month follow-up 2.94% 2.00% 5.56% 0.44
Last visit 7.14% 8.57% 3.57% 0.39
Optic nerve head CVs
Any visit 51.35% 48.08% 59.09% 0.39
Baseline 13.59% 12.00% 17.86% 0.44
4-month follow-up 11.76% 10.00% 16.67% 0.45
Last visit 35.79% 30.88% 48.15% 0.11
Abbreviations: CRVO, central retinal vein occlusion; CV, collateral vessel; DM, diabetes mellitus; NVA, neovascularization of the angle;
NVI, neovascularization of the iris.
a
P-value comparing CRVO eyes with DM to CRVO eyes without DM.
Influence of diabetes and diabetes type on CRVO
JG Santiago et al
7
Eye
Summary
What was known before
KFollowing diabetic retinopathy, central retinal vein
occlusion (CRVO) is the most frequently occurring retinal
vascular disease with estimated prevalence of between
0.1% and 0.8% and a 15-year cumulative incidence of
0.5%. The development of retinal ischemia is primarily
responsible for the ocular complications in CRVO.
KPatients with diabetes are thought to have an increased
risk for developing CRVO. However, little is known
regarding how diabetes and diabetes type contribute to
retinal outcomes in CRVO.
What this study adds
KOur data on over 19 000 patients show that diabetes
and diabetes type significantly influence ocular outcomes
in patients with CRVO.
KDiabetes was associated with increased risk of retinal
neovascularization and the need for panretinal laser
photocoagulation (PRP) following CRVO. Furthermore,
patients with type 1 diabetes were at eightfold higher
risk for developing neovascularization, twice as likely to
receive PRP and half as likely to develop optic nerve head
collateral vessels following CRVO as compared with
patients with type 2 diabetes and CRVO. Nevertheless,
final visual acuity outcomes were similar.
Conflict of interest
The authors declare no conflict of interest.
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Influence of diabetes and
diabetes type on anatomic and
visual outcomes following
central rein vein occlusion
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1.According to the retrospective chart review by Dr. Santiago
and colleagues, which of the following statements about the
prevalence of central retinal vein occlusion (CRVO) in
diabetic and nondiabetic patients is correct?
A The prevalence of CRVO was 0.5% in diabetic patients and
0.4% in nondiabetic patients
B In this cohort, rates of CRVO in diabetic and nondiabetic
patients were significantly higher than those in previously
published population-based studies
C Coexisting diabetes has been reported in more than half of
patients with CRVO
D Prevalence of bilateral CRVO was significantly higher in
diabetic vs nondiabetic patients
2.Your patient is a 66-year-old man with type 1 diabetes and
CRVO. According to the retrospective chart review by
Dr. Santiago and colleagues, which of the following
statements about ocular outcomes after CRVO in diabetic
vs nondiabetic patients is correct?
A Disc neovascularization occurred in 30% of diabetic
patients and 12% of nondiabetic patients
B Nearly half (48.7%) of diabetic patients underwent
panretinal photocoagulation (PRP)
C Rates of PRP were not significantly different in diabetic vs
nondiabetic patients
D Diabetic patients had significantly worse visual acuity
than nondiabetic patients
3.According to the retrospective chart review by Dr. Santiago
and colleagues, which of the following statements about
ocular outcomes after CRVO in patients with type 1 diabetes
vs those with type 2 diabetes would most likely be correct?
A Compared with patients with type 2 diabetes, those with
type 1 were at twice the risk for the development of
neovascularization
B Compared with patients with type 2 diabetes, those with
type 1 were not significantly more likely to need PRP
C Final visual acuity outcomes were significantly worse in
patients with type 1 diabetes vs those with type 2 diabetes
D After CRVO, patients with type 1 diabetes should
be monitored closely for development of retinal complica-
tions and need for treatment
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Influence of diabetes and diabetes type on CRVO
JG Santiago et al
10
Eye
