25 OS OD: Progression of Diabetic Retinopathy in The Hypertension Intervention Nurse Telemedicine Study

Letters
Figure. Intraocular Pressure Before, During, and After Glucosamine

Supplementation
A
OS
25
OD
24
23
IOP, mm Hg
22
21
20
19
18
17
16
worsening diabetic retinopathy.2 Despite pharmacologic improvements, hypertension remains poorly controlled in approximately half of Americans with it.3 The Hypertension Intervention Nurse Telemedicine Study (HINTS) investigated a
telemedicine-mediated medication management and behavioral intervention for hypertension. Participants in HINTS (including nondiabetic individuals) with poor BP control who received combined medication and behavioral management
demonstrated mean decreases in systolic BP of 15 mm Hg and
8 mm Hg at 12 and 18 months, respectively.4 The purpose of
the current analysis was to determine whether the interventions influenced the progression of diabetic retinopathy in participants with diabetes.
15
GI
D/C
25
24
23
IOP, mm Hg
22
21
20
19
18
17
16
15
GI
D/C
GI
D/C
25
24
23
IOP, mm Hg
22
21
20
19
18
17
16
15
Intraocular pressure (IOP) from patients in cohort A (n = 11) (A), cohort B (B),
and cohorts A and B combined (C) before glucosamine (V), during glucosamine
supplementation (Gl), and after discontinuing glucosamine (D/C).
4. Laurent TC, Laurent UB, Fraser JR. Functions of hyaluronan. Ann Rheum Dis.
1995;54(5):429-432.
5. Schachtschabel DO, Binninger E. Stimulatory effects of ascorbic acid on
hyaluronic acid synthesis of in vitro cultured normal and glaucomatous
trabecular meshwork cells of the human eye. Z Gerontol. 1993;26(4):243-246.
6. Covell LL. Glaucoma induced by systemic steroid therapy. Am J Ophthalmol.
1958;45(1):108-109.
Progression of Diabetic Retinopathy

in the Hypertension Intervention Nurse
Telemedicine Study
Interventions to improve glycemic control reduce the progression of diabetic retinopathy.1 Additionally, pharmacologic reduction of blood pressure (BP) in patients with diabetes mellitus and poorly controlled hypertension reduces the risk of
Methods | Eligibility criteria for HINTS included veterans having hypertension with inadequate BP control (average BP in past
12 months >140/80 mm Hg). Patients were excluded for hemodialysis or a creatinine level greater than 2.5 mg/dL (to convert
to micromoles per liter, multiply by 88.4). All participants received home BP monitors. Participants were randomized to the
following: (1) usual care; (2) nurse-administered behavioral intervention; (3) nurse-administered medication management; or
(4) a combination of the 2 interventions (Table). In institutional review boardapproved secondary analyses of diabetic
participants, a single chart abstractor (K.W.M.) determined the
presence and severity of diabetic retinopathy at baseline and the
most recent follow-up, as recorded by the eye care provider of
record in the electronic chart. Eligible participants had at least
1 documented dilated examination prior to or within 2 months
of enrollment and at least 1 subsequent dilated examination 365
days or later following enrollment. Progression was defined as
one or both eyes moving 1 or more steps along the spectrum of
retinopathy: none, mild nonproliferative, moderate nonproliferative, severe nonproliferative, proliferative, and visual acuity less than 20/60 in the better-seeing eye. Logistic regression
was used to examine the association between progression of diabetic retinopathy and the intervention group, adjusting for baseline hypertension control and duration of follow-up.
Results | Of the 593 veterans enrolled in HINTS, 252 were identified as diabetic. Of the 194 participants meeting the additional
criteria for documented eye examinations, 58 (30%) had diabetic retinopathy at baseline and 65 (34%) experienced progression of retinopathy in at least 1 eye at follow-up (mean [SD] followup, 1255 [344] days; median follow-up, 1310 days). After
controlling for duration of follow-up, the odds of diabetic retinopathy progression were significantly greater among participants receiving usual care than among participants receiving
medication management, either alone or in combination with
behavioral management (odds ratio = 2.16; 95% CI, 1.03-4.52;
P = .04), but not different from the group receiving behavioral
management alone (odds ratio = 0.88; 95% CI, 0.40-1.95; P = .84).
Discussion | A nurse-administered medication management program facilitated by home BP monitoring was associated with
decreased risk of progression of retinopathy in diabetic individuals with comorbid hypertension. Although intensive pharmacologic control of systolic BP (<120 mm Hg) may not be pro-
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JAMA Ophthalmology July 2013 Volume 131, Number 7
957
Letters
Table. Characteristics of Subjectsa

Randomization Group
Characteristic
Usual Care
(n = 49)
Medication
Management
(n = 48)
Behavioral
Management
(n = 50)
Medication and
Behavioral Management
Combination
(n = 47)
Sex, No.
Male
Female
48
45
50
43
23
20
23
25
Diabetes was defined as

self-reported history of diabetes or
diagnosis of diabetes listed in the
medical record.
Two subjects in the nonwhite

category self-identified as American
Indian and the remainder identified
as African American.
Defined as documented before or

within 2 months of study
enrollment.
Defined as progression from

absence to presence or less severe
to more severe from the time of
enrollment to the most recent
follow-up 365 days or later
following enrollment.
Race, No.
White
Nonwhiteb
Follow-up, mean (SD), d
26
28
27
32
1265 (385)
1219 (368)
1245 (311)
1292 (309)
Presence at baselinec
15 (31)
16 (33)
16 (32)
11 (23)
Progression, No. (%)d
20 (41)
11 (23)
22 (44)
12 (26)
Diabetic retinopathy in either eye,

No. (%)
tective against worsening diabetic retinopathy,5 the more

moderate reduction in systolic BP achieved in HINTS via the
nurse-administered telemedicine program4 (8 mm Hg lower
in the combined intervention group vs the control group) may
offer greater benefit. Telemedicine also has the potential advantage of reaching patients with suboptimal access to traditional care. Diabetic individuals with renal disease were excluded from HINTS, likely limiting the population to diabetic
individuals with less severe retinopathy. As such, the results
of this study are consistent with other work suggesting that
BP control is most helpful in controlling diabetic retinopathy
in early disease.6 Although as a secondary analysis this study
is limited in the ability to support causation (for example, less
progression of retinopathy in the combined intervention group
may be related to the intervention but not a direct result of decreasing BP), the potential benefit of telemedicine interventions targeting BP control in patients at risk for diabetic eye disease is encouraging and warrants further study.
Kelly W. Muir, MD, MHS
Janet Grubber, MSPH
Prithvi Mruthyunjaya, MD
Felicia McCant, MSSW
Hayden B. Bosworth, PhD
Author Affiliations: Durham VA Medical Center, Health Services Research and
Development, Duke University Medical Center, Durham, North Carolina (Muir,
Grubber, McCant, Bosworth); Department of Ophthalmology, Duke University
Medical Center, Durham, North Carolina (Muir, Mruthyunjaya); Departments of
Medicine and Psychiatry, School of Nursing, Duke University Medical Center,
Durham, North Carolina (Bosworth)
Corresponding Author: Dr Muir, Department of Ophthalmology, Duke University
Medical Center, PO Box 3802, Durham, NC 27710 (kelly.muir@duke.edu).
Published Online: May 23, 2013. doi:10.1001/jamaophthalmol.2013.81.
Conflict of Interest Disclosures: None reported.
Trial Registration: clinicaltrials.gov Identifier: NCT00129103.
1. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial
intervention and cardiovascular disease in patients with type 2 diabetes. N Engl
J Med. 2003;348(5):383-393.
2. UK Prospective Diabetes Study Group. Tight blood pressure control and risk
of macrovascular and microvascular complications in type 2 diabetes: UKPDS
38. BMJ. 1998;317(7160):703-713.
958
3. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment,

and control of hypertension, 1988-2008. JAMA. 2010;303(20):2043-2050.
4. Bosworth HB, Powers BJ, Olsen MK, et al. Home blood pressure
management and improved blood pressure control: results from a randomized
controlled trial. Arch Intern Med. 2011;171(13):1173-1180.
5. Chew EY, Ambrosius WT, Davis MD, et al; ACCORD Study Group; ACCORD
Eye Study Group. Effects of medical therapies on retinopathy progression in
type 2 diabetes. N Engl J Med. 2010;363(3):233-244.
6. Stratton IM, Kohner EM, Aldington SJ, et al. UKPDS 50: risk factors for
incidence and progression of retinopathy in type II diabetes over 6 years from
diagnosis. Diabetologia. 2001;44(2):156-163.
Long-term Suppression of Multidrug-Resistant

Cytomegalovirus Retinitis With Systemically
Administered Leflunomide
Cytomegalovirus (CMV) infection continues to affect outcomes in transplant recipients. Typical CMV antivirals, including ganciclovir sodium and its oral prodrug valganciclovir hydrochloride, foscarnet sodium, and cidofovir, are DNA
polymerase inhibitors. Resistance of CMV to this class of drugs
is an ongoing challenge. Alternative CMV antivirals include
leflunomide and cytomegalovirus immunoglobulin.1-3
We report the follow-up of a renal transplant recipient who
developed bilateral ganciclovir-resistant CMV retinitis that has
been treated with leflunomide since July 2004.4
Report of a Case | In March 2002, a 43-year-old CMV IgG
negative woman underwent cadaveric renal transplantation
from a CMV IgGpositive donor. Despite valganciclovir prophylaxis, she developed CMV viremia with retinitis. She was
placed on treatment doses of valganciclovir and was stable for
14 months. At month 18 following transplantation, she developed bilateral uveitis and reactivation CMV retinitis.
She was referred to the infectious diseases clinic at the University of Colorado and was initially treated with intravenous
ganciclovir and CMV immunoglobulin. Intravenous foscarnet, oral valganciclovir, and weekly CMV immunoglobulin were
initiated, with remission of the retinitis. Subsequent reactivation retinitis was treated with ganciclovir implantation5 without response. Weekly bilateral intraocular foscarnet injections were successful in the right eye only. Genotyping of the
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Letters

Figure. Intraocular Pressure Before, During, and After Glucosamine

Progression of Diabetic Retinopathy

Downloaded From: http://archopht.jamanetwork.com/ by Anisa Rahmawati on 04/23/2015

JAMA Ophthalmology July 2013 Volume 131, Number 7

Table. Characteristics of Subjectsa

Diabetes was defined as

Two subjects in the nonwhite

Defined as documented before or

Defined as progression from

Progression, No. (%)d

Diabetic retinopathy in either eye,

tective against worsening diabetic retinopathy,5 the more

3. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment,

Long-term Suppression of Multidrug-Resistant

JAMA Ophthalmology July 2013 Volume 131, Number 7

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