4_07_14

1. CLINICAL COURSE OF VITREOMACULAR
ADHESION MANAGED BY INITIAL
OBSERVATION
VISHAK J. JOHN, MD,* HARRY W. FLYNN, JR., MD,* WILLIAM E. SMIDDY, MD,*
ADAM CARVER, MD,† ROBERT LEONARD, MD,† HOMAYOUN TABANDEH, MD,‡
DAVID S. BOYER, MD‡
Purpose: The purpose of the study was to investigate the clinical course of patients with
idiopathic vitreomacular adhesion (VMA).
Methods: A noncomparative case series of patients who had clinical symptoms and
spectral-domain optical coherence tomography findings consistent with VMA. The VMA
was graded based on the optical coherence tomography findings at initial and follow-up
examinations. Grade 1 was incomplete cortical vitreous separation with attachment at the
fovea, Grade 2 was the Grade 1 findings and any intraretinal cysts or clefts, and Grade 3
was the Grade 2 findings and the presence of subretinal fluid.
Results: One hundred and six eyes of 81 patients were identified as having VMA by
spectral-domain optical coherence tomography at 3 retina clinics. The mean age was 73 years
and the mean time of follow-up was 23 months. Forty-three eyes (41%) had Grade 1 VMA, 56
eyes (52%) had Grade 2 VMA, and 7 eyes (7%) had Grade 3 VMA. By the last follow-up,
spontaneous release of VMA occurred in 34 eyes (32%), and pars plana vitrectomy was
performed in 5 eyes (4.7%). Mean best-corrected visual acuity was 0.269 logarithm of
the minimum angle of resolution or 20/37 at baseline (range, 20/20–20/200) and logarithm of
the minimum angle of resolution 0.251 or 20/35 at the last examination (range, 20/20–20/400).
Conclusion: In this selected patient cohort with mild symptoms, the clinical course of
patients with VMA managed by initial observation was generally favorable.
RETINA 34:442–446, 2014
The clinical and spectral-domain optical coherence
tomography (SD-OCT) features of vitreomacular
traction (VMT) syndrome have been described previ-
ously.1,2
Typical symptoms include decreased vision,
central metamorphopsia, photopsia, and micropsia.
The emergence of SD-OCT has demonstrated that
incomplete separation of the posterior vitreous with
persistent attachment confined to the fovea is more
common than is clinically symptomatic. The subset
of eyes with adhesion limited to the fovea may be
clinically distinct from eyes with broader zones of
vitreomacular adhesion (VMA) and has been termed
vitreofoveal adhesion or focal VMA.3–7
The SD-OCT
allows documentation of the baseline and ongoing
effects and extent of VMA, specifically those with
central visual symptoms associated with VMA.3,4,8,9
Vitreous adhesion and presumed traction have addi-
tionally been hypothesized to have a role in the
pathogenesis of many macular conditions, including
neovascular age-related macular degeneration, macu-
lar hole, and diabetic macular edema.10–12
The purpose of this study was to investigate the
clinical course of patients with VMA defined by
SD-OCT imaging, and followed with noninterventional
management. A classification of VMA based on the
SD-OCT findings is proposed as part of this study.
From the *Department of Ophthalmology, Bascom Palmer Eye
Institute, University of Miami Miller School of Medicine, Miami,
Florida; †Department of Ophthalmology, Dean McGee Eye Institute,
University of Oklahoma School of Medicine, Oklahoma City,
Oklahoma; and ‡Retina-Vitreous Associates Medical Group, Los
Angeles, California.
Supported in part by the National Institutes of Health (NIH),
Bethesda, MD, Grant NIH P30-EY014801 and an unrestricted
grant to the University of Miami from Research to Prevent Blind-
ness, New York, NY.
V. J. John and A. Carver have no financial/conflicting interests to
disclose. H. W. Flynn: Santen, Vindico; W. E. Smiddy: Alimera Sci-
entific; R. Leonard: Regeneron; H. Tabandeh: Alcon, Allergan, Bausch
& Lomb; D. S. Boyer: Aeripo, Alcon, Allegro, Allergan, Bausch &
Lomb, Bayer, Genentech, GSK, Merck, Neurotech, Novartis, Ophthal-
micsORA, Pfizer, Inc., QLT, Inc., Regeneron Pharmaceuticals.
Reprint requests: Harry W. Flynn, Jr., MD, 900 NW 17 Street,
Miami, FL 33136; e-mail: hflynn@med.miami.edu
442

2. Patients and Methods
The study design was a noncomparative case series
of patients for whom observational management was
recommended at the initial examination by vitreoreti-
nal surgeons at three centers. Symptomatic patients
with VMA localized to the fovea, noted on SD-OCT,
were identified and included in this study by virtue of
an intention not to treat them based on either good
presenting visual acuity or minimal symptoms. Fellow
eyes of the patients with macular hole and advanced
macular diseases (neovascular age-related macular
degeneration and diabetic macular edema) affecting
vision were excluded from the current study.
Patient demographics and histories including age,
gender, symptoms, best-corrected visual acuity
(BCVA), and duration to last follow-up examination
were recorded. The lens status and previous eye
surgeries including intravitreal injections were also
noted. The SD-OCT images at the initial and last visits
were retrospectively placed into 3 categories that
morphologically seemed to represent a spectrum of
progressive traction (Figure 1). Grade 1 was incom-
plete cortical vitreous separation with attachment at the
fovea, Grade 2 was Grade 1 and intraretinal cysts or
clefts, and Grade 3 was Grade 2 with the presence of
subretinal fluid. Statistical analysis using chi-square,
analysis of variance, and paired t-tests was performed
on the study data.
Results
One hundred and six eyes of 81 patients were
included. The cohort included 33 men (41%) and
48 women (59%). The mean age of the patients was
72.7 years with a range of 41 years to 92 years at the
initial visit. The mean BCVA was 0.269 logarithm of
the minimum angle of resolution (20/37). The median
time of follow-up was 18 months with a range of
1 month to 91 months. Previous interventions included
intraocular surgery in 43 eyes (some patients had
multiple previous procedures), including 37 eyes
(35%) with cataract surgery with intraocular lens
placement, 2 eyes (2%) with combined cataract and
glaucoma surgery, 3 eyes (3%) with panretinal
photocoagulation, and 4 eyes (4%) undergoing intra-
vitreal injections. Sixty-seven patients (63%) were
phakic at the time of initial visit, and 39 patients (37%)
were pseudophakic.
Using the study classification criteria (Figure 1),
43 eyes (41%) had Grade 1 VMA, 56 eyes (52%)
had Grade 2 VMA, and 7 eyes (7%) had Grade 3
VMA at the initial visit. The clinical course of
SD-OCT findings is summarized in Tables 1 and 2.
In Grade 1 eyes, the VMA released spontaneously on
the OCT in 13 eyes (30%), was unchanged in 23 eyes,
while the attachment progressed into a Grade 2 or 3 in
7 eyes. In Grade 2 eyes, VMA released spontaneously
in 17 eyes (30%), remained unchanged in 31 eyes, and
progressed to Grade 3 in 8 eyes, including 3 eyes that
developed full-thickness macular hole, leading to sur-
gery. Finally, within Grade 3 eyes, VMA released in
Fig. 1. Grades of VMA based on the SD-OCT findings in the study of
patients managed by initial observation. A. Grade 1: incomplete separa-
tion of cortical vitreous with persistent vitreous attachment at the fovea
and internal limiting membrane. B. Grade 2: Grade 1 + any intraretinal
cyst, cleft, or schisis. C. Grade 3: Grade 2 + neurosensory elevation of the
retina from retinal pigment epithelium (subretinal fluid).
COURSE OF VITREOMACULAR ADHESION JOHN ET AL 443

3. 4 eyes (57%), 1 eye improved to Grade 1, 1 eye
remained unchanged, and 1 eye progressed to a full-
thickness macular hole, prompting surgery. Thus, at
the last examination, overall 34 eyes (32%) had spon-
taneously resolved VMA, 25 eyes (23%) had Grade 1
VMA, 38 eyes (36%) had Grade 2 VMA, 4 eyes (4%)
had Grade 3 VMA, and 5 eyes (5%) underwent pars
plana vitrectomy (PPV). The differences in spontane-
ous resolution rates for the various grades were not
significant (P = 0.35). Similarly, the rates of worsening
anatomy in all presenting VMA grades were equiva-
lent (P = 0.64).
All but 5 of the 106 eyes were observed throughout
the study. Those 5 patients (4.7%) underwent PPV
(4 eyes for development of full-thickness macular
holes, and one for progressive loss of vision from
VMA). Four of the operated eyes were Grade 2 at
initial visit, while one was Grade 3 at baseline. After
vitrectomy, the mean visual acuity at last follow-up in
the operated eyes was logarithm of the minimum angle
of resolution 0.30 or 20/40 (20/30, 20/30, 20/40, and
20/100 in the 4 patients with macular hole, and 20/25
in the patient operated for worsening VMA). At the
last examination, all four patients with macular hole
had successful closure and the progressive patient with
VMA had improved foveal anatomy (resolution of
retinal cyst and subretinal fluid).
The BCVA among three VMA grades at presenta-
tion was significantly different (P = 0.012), with Grade
3 patients having the worst visual acuity at the initial
visit. There were no significant differences between
changes from the initial to the final mean BCVA in
each of the 3 VMA grades (Table 1). At the last exam-
ination, the mean BCVA in the observation group
(excluding the 5 operated patients) was 0.251 loga-
rithm of the minimum angle of resolution (20/35),
which was similar to the baseline visual acuity.
Discussion
The main finding of this study is that the observa-
tional management of at least milder grades of VMA is
a favorable initial option. The current study demon-
strated stability of BCVA between the initial and last
examinations, a high rate of spontaneous VMA release
(32%), and a low rate of progression to a more severe
anatomical configuration (16%). A grading scheme for
VMA based on the SD-OCT features was also useful
for clinical monitoring by better defining subgroups in
the current study and may be useful for standardizing
the observations and outcomes in future studies.
Debate about whether persistently attached vitreous
always represents actual traction has led to the use of
the terms, VMT or VMA. The Microplasmin for
Intravitreal Injection-Traction Release Without Surgi-
cal Treatment (MIVI-TRUST) investigators used the
term VMT when there were visual symptoms associ-
ated with VMA.13
The patients in that study repre-
sented relatively small zones of VMA, limited to the
fovea as documented by the OCT. In the pre-OCT era,
only patients with relatively advanced VMA, as
observed by slit-lamp biomicroscopy, were clinically
recognizable. These were categorized according to the
Table 1. Visual Acuity at Presentation and at the Last Follow-up for Each Grade of VMA in the Study of Patients Managed
by Initial Observation
Presenting VMA Grade No. Eyes
Mean LogMAR (SD) at
Presentation
Mean LogMAR (SD) at
the Last Examination P*
Grade 1 43 0.21 (0.18) 0.21 (0.19) 0.88
Grade 2 56 0.30 (0.20) 0.32 (0.28) 0.54
Grade 3 7 0.43 (0.31) 0.34 (0.30) 0.34
*Paired t test.
LogMAR, logarithm of the minimum angle of resolution; SD, standard deviation; VMA, vitreomacular adhesion.
Table 2. Final Status of VMA in the Study of Patients Managed by Initial Observation
Presenting VMA Grade No. Eyes Improved (%)* Stable (%)† Worse (%)‡
Grade 1 43 13/43 (30) 23/43 (53) 7/43 (16)
Grade 2 56 17/56 (30) 31/56 (55) 8/56 (14)
Grade 3 7 4/7 (57) 1/7 (14) 2/7 (28)
*Improved: release of VMA.
†Stable: VMA is still present, and no change.
‡Worse: progression from Grade 1 to Grade 2 or Grade 3, OR, progression from Grade 2 to Grade 3 or a macular hole or surgery, OR,
progression from Grade 3 to a macular hole or surgery.
VMA, vitreomacular adhesion.
444 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES 2014 VOLUME 34 NUMBER 3

4. extent of the persistent vitreous attachment only as
observed by slit-lamp biomicroscopy.14
This subset
was deduced to be more likely to progress and surgical
intervention was proposed.15–17
Initially, the rationale
for surgery was to avert macular hole formation,18
but
subsequent clinical experience demonstrated that
releasing apparent traction allowed partial normaliza-
tion of anatomy and function in more clinically severe
cases. In a retrospective case series of 36 patients
undergoing PPV for VMA, Davis et al19
demonstrated
favorable visual outcomes (50% improved visual
acuity by $2 lines). In a pre-OCT era study, in 53
symptomatic VMA eyes (diagnosed clinically) with
a median follow-up of 5 years, most (64%) had
a decrease in visual acuity over time. Better visual
acuity and resolution of cystoid edema on fluorescein
angiography were noted in 11% of the patients in the
study who underwent a complete posterior vitreous
detachment.14
These findings seemed to justify surgi-
cal intervention in more severe VMA cases.
The OCT allows more precise means for categori-
zation and longitudinally monitoring of such patients.
Chan et al20
classified a subset of VMA on OCT as
Stage 0 macular holes and postulated it as a group at
risk for developing macular holes in the fellow eyes.
Additionally, Gaudric et al16
documented the progres-
sion of VMA to full-thickness macular holes using
OCT in fellow eyes of some patients with macular
hole.16
A 2012 OCT study of eyes with tractional
cystoid macular edema secondary to VMT reported
a complete and spontaneous posterior vitreous detach-
ment in 53% of eyes.21
However, the clinical course of patients with VMA is
not well established, especially when the degree of
visual loss is mild. The SD-OCT has identified many
more patients with earlier, minimal, or mild visual loss
symptoms,4,9
making indications for the management
of milder cases even less clear. Many such patients
remain stable without surgical intervention, but the nat-
ural history is not well established.1
The 32% rate of
spontaneous VMA resolution in the current study might
be even higher with longer follow-up. The relatively
favorable anatomical course was commensurated with
the stable mean BCVA for patients in the current study
(0.269 logarithm of the minimum angle of resolution
initially and 0.251 logarithm of the minimum angle of
resolution at the last follow-up examination).
Surgical treatment consisting of PPV with a release
of the vitreofoveal attachment, and possibly with
consideration of internal limiting membrane peeling,
has been the contemporary interventional option
for VMA.15,17
Chan et al22
described the induction
of a posterior vitreous detachment by injecting an
expansile gas as a treatment for impending macular
holes in the early 1990s,22
but few clinicians adopted
that technique since that time. Recently, Rodrigues
et al23
reported 40% rate of the VMA release at 1
month after a single injection of expansile perfluoro-
propane (C3F8), confirmed by SD-OCT. With very
little adverse effects reported in the study, and the
relatively low cost of the gas bubble, this pneumatic
vitreolysis could be an alternative to the more invasive
surgical option of PPV.23,24
Approved in 2012 by the
Food and Drug Administration, a pharmacologic inter-
vention with the intravitreal injection of microplasmin
for the release of symptomatic VMA has been intro-
duced for patients with visual loss to 20/25 or worse.
In patients with VMT, 10% of patients injected with
saline had a release of vitreofoveal adhesion at 28 days
compared with 26.5% of patients injected with micro-
plasmin.13
It is possible that vitreoretinal surgeons
may use this pharmacologic option in the more severe
VMA cases rather than less symptomatic milder cases,
in an attempt to avoid the need for future PPV. Con-
versely, they may also use it to treat patients with milder
symptoms and less extensive VMA so as to halt pro-
gression and avoid PPV. The ability of microplasmin to
induce posterior vitreous detachments and its use in
managing small macular holes with VMA has been
demonstrated through the MIVI trials.13
However, its
value in eyes with good vision and minimal symptoms
is less clearly defined. The 32% spontaneous VMA
release rate in the current study compared favorably
with the rate in the MIVI-TRUST study, raising ques-
tions as to the value of ocriplasmin in milder cases.
The limitations of the current study include its
retrospective nature, relatively few patients, and
potential bias in that the individual attending physician
made the decision to assign patients to observational
management. Patients with both VMA and early
macular holes were not included in the current study.
Patients with VMA with more severe visual symptoms
were likely managed with PPV and, therefore, were
not included in the study. In contrast, patients with
better visual acuity and minimal symptoms were
selected by the study investigators for observational
management. Thus, the study cohort may have
represented a milder or at least different group of
patients with VMA compared with MIVI-TRUST.
In conclusion, the present study demonstrates that the
clinical course of patients with relatively mild symp-
tomatic VMA is often favorable during follow-up.
Hence, patients with VMA diagnosed by SD-OCT
but with minimal or nonprogressive symptoms can be
initially considered for noninterventional management.
Key words: vitreomacular traction, vitreofoveal
adhesion, microplasmin, macular hole.
COURSE OF VITREOMACULAR ADHESION JOHN ET AL 445

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