5. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Central Retinal Vein Occlusion
• Central retinal vein occlusion (CRVO) is a retinal vascular
condition that may cause significant ocular morbidity. It
commonly affects men and women equally and occurs
predominantly in persons over the age of 65 years. In this
population there may be associated systemic vascular
disease, including hypertension and diabetes. Younger
individuals who present with a clinical picture of CRVO may
have an underlying hypercoagulable or inflammatory
etiology. Population-based studies report prevalence of
CRVO at <0.1 to 0.4%.
6. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Central Retinal Vein Occlusion
• CRVO is usually a unilateral disease; however, the annual risk of
developing any type of retinal vascular occlusion in the fellow eye is
approximately 1% per year, and it is estimated that up to 7% of
persons with CRVO may develop CRVO in the fellow eye within 5
years of onset in the first eye. Individuals with CRVO demonstrate a
significant decrease in vision-related quality of life with increased
healthcare costs and resource use as compared to a reference
group without ocular disease. CRVO may impact a person’s ability
to perform activities of daily living, especially in cases of bilateral
CRVO or when concurrent ocular disease limits vision in the fellow
eye.
9. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CLINICAL FEATURES
• CRVO usually presents with sudden painless loss of vision, but it may
also present with a history of gradual visual decline that may correlate
with a series of less severe occlusions. The typical clinical constellation
in CRVO includes retinal hemorrhages (both superficial flame-shaped
and deep blot type) in all four quadrants of fundus with a dilated,
tortuous retinal venous system. The hemorrhages radiate from the optic
nerve head, are variable in quantity, and may result in the classic “blood
and thunder” appearance . Optic nerve head swelling, cotton-wool
spots, splinter hemorrhages, and macular edema are present to varying
degrees . Breakthrough vitreous hemorrhage may also be observed.
10. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CLINICAL FEATURES
•With time, the extent of retinal hemorrhage
may decrease or resolve completely with
variable degrees of secondary RPE
alterations. The time course for resolution of
the hemorrhages varies and is dependent on
the amount of hemorrhage produced by the
occlusion. Macular edema often chronically
persists despite resolution of retinal hges .
11. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CLINICAL FEATURES
• An epiretinal membrane may also form.
Optociliary shunt vessels can develop on the optic
nerve head, a sign of newly formed collateral
channels with the choroidal circulation . NVD &
NVE may develop as a response to secondary
retinal ischemia. The vessels that comprise NVD
are typically of smaller caliber than optociliary
shunt vessels, branch into a vascular network
resembling a net, and will leak on FA .
Fibrovascular proliferation from NVD or NVE may
result in vitreous hemorrhage or TRD .
14. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CLINICAL FEATURES
•Of those with initial visual acuity of 20/40 or
better, the majority maintained this acuity.
Individuals with intermediate visual acuity
(20/50–20/200) had a variable outcome: 21%
improved to better than 20/50, 41% stayed in
the intermediate group, and 38% were worse
than 20/200. Persons with poor visual acuity
at onset (less than 20/200) had only a 20%
chance of improvement .
15. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CLINICAL FEATURES NVI / NVA
• Anterior-segment findings may include iris and/or angle
neovascularization (NVI/NVA). NVI typically begins at pupillary
border but may extend across the iris surface. NVA is detected
during undilated gonioscopy as fine branching vessels bridging the
scleral spur and may develop without any NVI in 6–12% of eyes
with CRVO. The CVOS used an index of any 2 clock-hours of NVI
or any NVA as evidence of significant anterior-segment NV , which
was found in 16% of eyes with 10–29 disc areas of angiographic
nonperfusion and 52% of eyes with 75 disc areas or more of
angiographic nonperfusion.
16. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CLINICAL FEATURES
• In the CVOS, worse initial visual acuity correlated
with the development of NVI / NVA: 5% in eyes
with 20/40 or better, 14.8% in eyes with 20/50–
20/200, and 30.8% in eyes with worse than 20/200
acuity. Long-standing NVA may lead to secondary
angle closure from peripheral anterior synechiae
formation.
• Elevated IOP associated with NVI/NVA is the
hallmark of NVG .
18. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
PERFUSION STATUS
• The CVOS classified the perfusion status of a
CRVO as perfused, nonperfused, or
indeterminate based on fluorescein
angiographic characteristics. Angiographic
assessment of perfusion status in CRVO is
based on the photographic protocol from the
CVOS which used a conventional wide-angle
fundus camera with sweeps of the
midperiphery 30 seconds after intravenous
injection of sodium fluorescein .
21. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
PERFUSION STATUS
• A perfused CRVO (also termed nonischemic, incomplete, or
partial) demonstrates less than 10 disc areas of retinal capillary
nonperfusion on angiography . These eyes typically have a
lesser degree of intraretinal hemorrhage on presentation.
Generally, eyes with perfused CRVO have better initial and final
visual acuity. A nonperfused CRVO (also termed ischemic,
hemorrhagic, or complete) demonstrates 10 or more disc areas
of retinal capillary nonperfusion on angiography . Acutely, these
eyes demonstrate a greater degree of intraretinal hemorrhage,
macular and disc edema, and capillary nonperfusion than in
perfused CRVO.
23. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
PERFUSION STATUS
• A CRVO is categorized as indeterminate when
there is sufficient intraretinal hemorrhage to
prevent angiographic determination of the
perfusion status. Other examination features that
may help in determining the perfusion status in
the acute phase of a CRVO include baseline
visual acuity, presence of an afferent pupillary
defect, electroretinography (a negative waveform
may be seen), and Goldmann perimetry.
24. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
PERFUSION STATUS
CVOS classification of initial perfusion status of the
CRVO was important for determining the natural history
of the disease. Poor visual acuity and large areas of
retinal capillary nonperfusion were significant factors
associated with an increased risk of developing
NVI/NVA. In eyes initially categorized as perfused, 10%
developed NVI/NVA compared to 35% of eyes initially
characterized as nonperfused or indeterminate. At 3
years, there was a 45% chance of developing
neovascular glaucoma after onset of ischemic CRVO.
26. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
PERFUSION STATUS
Overall, 34% of initially perfused eyes converted
to nonperfused status after 3 years. In the
CVOS, 38 eyes (83%) with an indeterminate
CRVO at baseline were ultimately determined to
be nonperfused. Initial visual acuity was highly
correlated with degree of nonperfusion - eyes
with nonperfused CRVO were much more likely
than those with perfused CRVO to have poor
visual acuity at initial presentation and final
visit.
28. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CLINICAL EVALUATION
• At the time of initial presentation, a careful assessment
of CRVO duration and the degree of macular edema and
retinal ischemia will determine treatment options and the
follow-up schedule. An ocular history may determine the
onset of the occlusion, although individuals may not have
noted vision loss if the fellow eye has maintained good
acuity. A history of systemic diseases, such as
hypertension, diabetes, and heart disease, and a
personal or family history of thrombosis or
hypercoagulable state should be determined.
29. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CLINICAL EVALUATION
• The ophthalmic examination should be performed
on both eyes and include visual acuity, pupillary
reaction, and IOP . Undilated slit-lamp examination
is performed to detect NVI or NVA. Undilated
gonioscopy is essential to determine the presence
of NVA or evidence of angle closure from
peripheral anterior synechiae, as NVA may be
present without any NVI in up to 12% of eyes.
30. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CLINICAL EVALUATION
• Ophthalmoscopic examination will help
differentiate a CRVO from intraretinal
hemorrhage associated with carotid
occlusive disease. Adjunctive imaging
studies, including OCT and FA , are helpful in
evaluating and following the presence of
macular edema and perfusion status.
31. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
THERAPEUTIC OPTIONS
• Treatment for CRVO is directed at treating the sequelae of CRVO,
particularly macular edema and neovascularization. The recent
development of intravitreal pharmacotherapy has revolutionized the
treatment of CRVO-associated macular edema . While these
intravitreal agents can also improve secondary neovascularization,
PRP remains definitive treatment. Alternative experimental therapies
have sought to modify anatomic alterations believed to be responsible
for CRVO. Of course, management of blood pressure and other
systemic factors is always of paramount importance.
33. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Treatment of macular edema
Observation
• The CVOS group M report studied the effect of grid
pattern argon laser photocoagulation to improve visual
acuity in 155 eyes with perfused CRVO-associated
macular edema and 20/50 acuity or worse. Laser
treatment involved a grid pattern in area of leaking
capillaries within 2 disc diameters of the foveal center
but not within the foveal avascular zone. At 36 months,
there was no significant difference in mean visual acuity
between treated (20/200) and untreated (20/160) eyes
despite reduction of angiographic macular edema.
34. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Treatment of macular edema
• Therefore, the CVOS did not
recommend grid laser for CRVO-
associated macular edema. In the
absence of robust treatment options
before the advent of intravitreal
pharmacotherapy for retina diseases,
standard of care for CRVO-associated
macular edema was observation.
35. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Steroids for Retinal Vein
Occlusion 2009
• The SCORE study compared the effects
of 1-mg and 4-mg intravitreal
triamcinolone acetonide (IVTA; Trivaris,
Allergan) to standard of care, which
was observation for CRVO and grid
laser for BRVO.
36. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
SCORE-CRVO
• In SCORE-CRVO, patients received an average of 2
injections of IVTA over the course of 1 year. At the
end of year 1, 27% percent of patients who
received 1-mg IVTA and 26% of patients who
received 4-mg IVTA achieved a visual acuity gain of
3 or more lines compared with only 7% of patients
in the observation group. The visual acuity was
sustained throughout year 2. The side-effect profile
for lower dose was more favorable, however,
indicating a higher level of safety for 1-mg dose.
37. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
The GENEVA trial published in
2010
• The GENEVA trial, published in 2010, examined the effects of the
dexamethasone intravitreal implant (Ozurdex, Allergan) in patients
with macular edema secondary to either BRVO or CRVO. The trial
enrolled 1267 patients and evenly divided them into 3 groups. The
first group received a 0.7-mg dexamethasone implant, the second
group received a 0.35-mg dexamethasone implant, and the third
group received a sham implant. The results of the study showed
that the dexamethasone implant was effective in treatment of
macular odema but with complications of cataract and glaucoma .
38. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
THE GENEVA TRIAL 2010
• IOP increases of 10 mm Hg or higher occurred in 32.6% of
patients; 33.7% had an IOP of 25 mm Hg or more at any
single visit, and 9.4% had an IOP of 35 mm Hg or more at
any single visit. This led to 29.1% of patients requiring
medication to lower increased IOP. In addition,1.4% and
1.7% of patients underwent glaucoma laser surgery and
glaucoma incisional surgery, respectively. Almost 16% of
patients underwent cataract extraction during the study
period. Most of these patients had some degree of lens
opacity at baseline .
39. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Intravitreal Anti-VEGF Agents for
Retinal Vein Occlusion
•The BRAVO and CRUISE studies, published
in 2010, evaluated the effects of
ranibizumab (Lucentis ) in patients with
macular edema secondary to BRVO and
CRVO, respectively. In both studies patients
were randomly assigned to receive monthly
injections of 0.3 mg or 0.5 mg ranibizumab
or sham injections for 6 consecutive months
41. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Intravitreal Anti-VEGF Agents for
Retinal Vein Occlusion
• At the sixth month, patients were followed monthly and reinjected as
needed. Also at the sixth month, patients that were in sham group
were allowed to cross over to the 0.5 mg ranibizumab group. After
month 12, patients were monitored on a quarterly basis until month
24 and reinjected accordingly. Reinjection criteria were based on
OCT findings of a central subfield thickness of at least 250 μm or
signs of intraretinal fluid. In the BRAVO study, macular grid laser
rescue treatment was allowed after month 3 and could be repeated
every 3 months.
42. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Intravitreal Anti-VEGF Agents for
Retinal Vein Occlusion
• In the first 6 months a rapid improvement in BCVA
(+18.3 letters for the 0.5 mg group, +16.6 letters
for the 0.3 mg group, and +7.3 letters for the
sham group; P < .05) that was statistically
significantly different from the sham group was
observed in both ranibizumab groups. There was
no difference between the ranibizumab groups. It
was noted that, at month 12, both ranibizumab
groups maintained the visual acuity gains of the
first 6 months .
43. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CRUISE trial
• The CRUISE trial had a design similar to the BRAVO
trial. The only difference was that no macular laser
treatment was allowed These results indicate that
as-needed (prn) quarterly dosing is not sufficient to
treat macular edema due to CRVO. It appears that
some eyes stabilize after a few monthly injections
and require a few injections thereafter, but vast
majority require frequent follow-up and multiple
injections to control macular edema .
44. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CRUISE trial
• Unlike in BRVO, the long-term outcomes in CRVO were
more guarded. Results from this study showed that 44% of
eyes had resolution of macular edema, 53% had an
improvement of 3 lines or more from CRUISE trial baseline,
and 44% of eyes had a BCVA of 20/40 or better. Eyes that
had resolution of macular edema had a statistically
significantly greater improvement in BCVA (25.2 letters vs
4.3 letters), and a statistically significantly greater
proportion achieved BCVA of 20/40 or better (64.3% vs
27.8%) compared with those eyes without resolution.
45. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CRVO
CRVO WITH MACULAR ODEMA
INVOLVING CENTRE OF RETINA
NO
OBSERVATION
YES
INTRAVITREAL AVASTIN .
STEROIDS MAY BE
CONSIDERED
FA
OBSERVATION FOR NVE & NVD & NVI
ESP IF CNP AREA MORE THAN 10 DD AREANO NVE
NVD, NVI
NVE,NVD OR NVI PRESENT
VITREOUS HGE & NVG
PRP + ARC
NO GRID LASER
46. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
PRPLaser photocoagulation
• The CVOS recommended that PRP be delivered promptly after the
development of NVI/NVA but not prophylactically in eyes with
nonperfused CRVO. In approximately 90% of cases, the regression
of NVI/NVA occurs within 1–2 months of PRP. Persistent
neovascularization after PRP should be followed closely, and
additional PRP may be applied in attempts to halt its progression.
Persons presenting with NVD/NVE without NVI/NVA should be
treated with PRP to prevent anterior-segment neovascularization.
Prophylactic placement of PRP may be considered in eyes with
nonperfused CRVO and risk factors for developing NVI/NVA (male
gender, short duration of CRVO, extensive retinal nonperfusion, and
extensive retinal hemorrhage) or in cases where frequent
ophthalmologic follow-up is not possible.
47. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CONCLUSION
• CRVO is a sight-threatening disease with
significant ocular morbidity, including macular
edema and ocular neovascularization. Before
recent advent of intravitreal pharmacotherapy
in management of CRVO, standard of care was
guided by results from CVOS, which
recommended observation of macular edema
and retinal ischemia with management of
neovascular sequelae using PRP .
48. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CONCLUSION
• More recently, intravitreal corticosteroids and particularly
anti-VEGF agents have demonstrated impressive
improvements in macular edema, visual acuity, and even
NV complications with a favorable side-effect profile. The
use of ranibizumab (Lucentis) and dexamethasone
implant (Ozurdex) have been FDA-approved for the
treatment of CRVO. Intravitreal pharmacotherapy has now
replaced observation as the standard of care for the
management of macular edema associated with CRVO.
BEVACIZUMAB ( AVASTIN) is used off label .
49. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CONCLUSION
• Results from another small study indicate that progression of retinal
nonperfusion continues, particularly in eyes in which macular edema has
not resolved.
• The authors of this study state that, in eyes with macular edema
secondary to RVO, the resolution of macular edema should not be the
sole treatment objective. The prevention of worsening retinal
nonperfusion should be a treatment objective as well. Periodic
fluorescein angiograms, preferably wide-angle, should be performed to
monitor perfusion status.
50. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CONCLUSION
• Despite the advances in pharmacologic therapy, many eyes with RVO
continue to lose vision. The common final pathway appears to be
photoreceptor cell death. Future research for RVO treatments may
focus on neuroprotective and photoreceptor regeneration therapies to
improve sight in patients who have limited vision due to RVO.
51. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CRVO
CRVO WITH MACULAR ODEMA
INVOLVING CENTRE OF RETINA
NO
OBSERVATION
YES
INTRAVITREAL AVASTIN .
STEROIDS MAY BE
CONSIDERED
FA
OBSERVATION FOR NVE & NVD & NVI
ESP IF CNP AREA MORE THAN 10 DD AREANO NVE
NVD, NVI
NVE,NVD OR NVI PRESENT
VITREOUS HGE & NVG
PRP + ARC
NO GRID LASER
53. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Neovascular Glaucoma
• Neovascular glaucoma (NVG) is a devastating
ocular disease often associated with poor
visual prognosis. It is a relatively common
complication of several retinal disorders,
especially CRVO, PDR , and ocular ischemic
syndrome. The pathophysiology of NVG involves
the formation of new blood vessels on the
surface of the iris and the angle of the anterior
chamber, which initially impedes aqueous
outflow, but later contracts to produce an
angle-closure form of glaucoma.
54. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Neovascular Glaucoma
• Currently used medical or surgical treatment
has a low success rate, which has been
improved by the adjunct use of IVB. The most
effective treatment involves retinal ablation,
which reduces the level of retinal hypoxia and
slows the subsequent angiogenic cascade. The
goal of treatment should be to catch disease
early and halt the angiogenic cascade to
prevent more serious consequences of NVG.
55. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Neovascular Glaucoma
• Approximately 36% of NVG occurs after CRVO,
32% with PDR, and 13% occurs after carotid
artery obstruction. Given that the underlying
etiology of developing NVG is some form of
retinal ischemia, it is more prevalent in elderly
patients who have significant cardiovascular
risk factors such as hypertension, diabetes,
dyslipidemia, and a history of smoking.
57. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
NVG IN CENTRAL RETINAL VEIN
OCCLUSION
• The predominant risk factor for the
development of neovascular complications
following central retinal vein occlusion (CRVO)
is the extent, location, and duration of retinal
ischemia (ischemic drive). Whereas anterior
segment neovascularization is rare in
nonischemic CRVO, the incidence of NVI is as
high as 60% in ischemic eyes, usually occurring
at a mean of 3–5 months after the CRVO.
58. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
NVG IN CENTRAL RETINAL VEIN
OCCLUSION
• The importance of closely following
patients with CRVO was demonstrated by
the landmark CVOS . The CVOS showed
that 15% of nonischemic CRVO could
proceed to ischemic CRVO in the first 4
months. During the next 32 months an
additional 19% of eyes were found to have
converted to the ischemic form for a total
of 34% after 3 years.
59. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
NVG IN CENTRAL RETINAL VEIN
OCCLUSION
•The development of nonperfusion or ischemia
was most rapid in the first 4 months and
progressed continuously throughout the
entire duration of follow-up. NVI of at least
two clock hours, and/or NVA developed in 16%
of eyes. The CVOS also found that the most
important risk factor predictive of rubeosis
iridis was poor visual acuity.
60. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
NVG IN CRVO
• In a prospective clinical and fluorescein
angiographic study of patients with CRVO, 20%
developed NVG. The eyes were classified as
having either ischemic or hyperpermeable type
of CRVO according to the extent of retinal
capillary nonperfusion demonstrated by initial
fluorescein angiogram. The risk of developing
NVG was approximately 60% in eyes with
extensive retinal ischemia.
61. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
NVG Etiology and Pathogenesis
• In ischemic retinal disease, hypoxia induces
production of vascular endothelial growth
factor (VEGF), a vasoproliferative substance,
which acts upon healthy endothelial cells of
viable capillaries to stimulate the formation of
fragile new vessels (neovascularization). In
cases of extreme retinal hypoxia, there are
essentially very few viable retinal capillaries
available.
62. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
NVG Etiology and Pathogenesis
• In that instance, VEGF is theorized to diffuse forward to
the nearest area of viable capillaries, namely the
posterior iris. Neovascularization buds off from the
capillaries of the posterior iris, grows along the posterior
iris, through the pupil, along the anterior surface of the
iris, and then into the angle. Once in the angle, the
neovascularization, along with its fibrovascular support
membrane, acts to both physically block the angle as well
as bridge the angle and pull the iris and cornea into
apposition, thus blocking the trabecular meshwork.
63. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Diagnosis and Ancillary Testing
• Clinicians should perform a comprehensive
ophthalmologic exam with particular attention to
the pupillary margin . An undilated slit-lamp
examination and gonioscopy are essential for the
detection of NVI and NVA. Although NVI usually
precedes NVA, new vessels may occasionally be
found in the angle without evidence of iris
neovascularization. Fluorescein angiography of the
anterior segment and fluorescein gonio-
angiography may be contributive to the diagnosis
of early rubeosis iridis .
66. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Signs and Symptoms
• Depending on the severity of intraocular pressure
elevation, intraocular inflammation, and
glaucomatous optic neuropathy, patients can
present with various signs and symptoms of NVG
that include decreased vision, photophobia, corneal
edema, conjunctival injection, rubeosis, elevated
intraocular pressure, inflammation, hyphema, and
vitreous hemorrhage. If the inflammation is severe,
or the elevation in IOP is acute, the patient may
exhibit severe pain, headache, nausea, and/or
vomiting.
67. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Stages of Neovascular Glaucoma
• The typical clinical presentation can be divided into three stages:
(1) rubeosis iridis; (2) open-angle glaucoma stage; and (3) angle-
closure glaucoma stage. These stages generally follow each other
in progression. The relevant clinical signs and symptoms are
included in this section and summarized in Table .
69. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
STAGE 1: RUBEOSIS IRIDIS
• At this stage tufts of rubeosis can be found at the pupillary
margin and/or rubeotic vessels may be found in the angle (Fig.
37-3). Although slit-lamp biomicroscopy can detect iris
neovascularization, iris fluorescein angiography has been
shown to be more reliable in detecting very early iris
neovascularization. Although neovascularization is usually seen
first at the peripupillary iris, a thorough gonioscopic examination
should be performed since NVA can sometimes precede
rubeosis.31 Intraocular pressure is typically normal, but can be
elevated if a preexisting open-angle glaucoma is present.
70. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
STAGE 2: OPEN-ANGLE GLAUCOMA
• At this stage, the IOP begins to rise and stays
elevated. The elevated IOP can also rise suddenly,
causing acute-onset glaucoma. Due to the fragile
nature of the new vessels, a hyphema can also
present at this stage. The degree of rubeosis iridis
is usually more prominent and the anterior chamber
can show some level of inflammation. Gonioscopy
typically shows an open angle, but NVA can be
significant.
71. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
STAGE 2: OPEN-ANGLE GLAUCOMA
• The NVI can be continuous with the new vessels in
the angle. Histopathologically, the hallmark of this
stage is growth of a fibrovascular membrane,
including rubeotic vessels on the iris surface that
extend over the trabecular meshwork, decreasing
aqueous outflow and increasing IOP in an
aberrantly open angle . Both inflammation in the
anterior chamber and possible hyphema can
exacerbate the disease process.
72. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
STAGE 3: ANGLE-CLOSURE GLAUCOMA
• The contraction of the fibrovascular membrane causes
progressive angle closure, ectropion uveae, peripheral anterior
synechiae formation, and a flat, glistening appearance to the
iris. Patients will often complain of photophobia, reduced visual
acuity, acute severe pain, headache, nausea, and/or vomiting.
Rubeosis is usually severe, with possible hyphema, moderate
inflammation, and IOP as high as 60–70 mmHg. Conjunctival
injection and corneal edema are frequently present.
Fundoscopic examination may reveal optic nerve cupping. The
glaucoma at this stage is severe and usually requires some
form of surgical intervention.
74. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Treatment Options
• The treatment of NVG varies depending on the stage of the
disease and the clarity of the media. Treatment strategies focus
on two separate but related issues: decreasing IOP and
reducing retinal ischemic drive.
75. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
TREATMENT OF
NEOVASCULARIZATION
• Once rubeosis iridis has begun, the primary goal of
treatment is to reduce the ischemic drive of
neovascularization. This is best accomplished with
panretinal photocoagulation (PRP) to destroy
ischemic retina, minimize the eye’s oxygen
demand, and reduce the amount of VEGF being
released. PRP tends to be effective in causing
regression and involution of anterior segment
neovascularization.
76. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
TREATMENT OF
NEOVASCULARIZATION
• In recent years, bevacizumab (Avastin [Genentech, Inc.]) has
emerged as an adjunct first-line treatment for rubeosis iridis.
Initial studies reported rapid regression of iris and angle
neovascularization in patients with NVG and refractory IOP
elevation . In the first large study using IVB, Wakabayashi et al.
showed that IVB combined with full PRP in patients with
rubeosis iridis may reduce risk of developing NVG. IVB
stabilized neovascular activity, and may help control IOP if the
angle is still open. If the angle was closed secondary to
synechiae, there was no effect on IOP.
77. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Slit-lamp photograph before use
of Avastin in a patient with NVG
78. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
fluorescein photograph before use of
Avastin in a patient with NVG
79. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Slit-lamp photograph after use
of Avastin in a patient with NVG
80. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
fluorescein photograph after use of
Avastin in a patient with NVG
83. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
TREATMENT OF NVG
• Once a patient has progressed beyond the early stages of
rubeosis iridis and has elevated IOP with an open- or closed-
angle glaucoma, the primary goals of treatment are to regress
any neovascularization as described above and control IOP.
84. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Medical Management of IOP
• If the angle is open and the eye still has relatively useful vision,
but IOP is above normal, initiate medical therapy to reduce
aqueous production. Patients may require a combination of
carbonic anhydrase inhibitors (topical or systemic), topical β-
blockers, and/or α2-agonists to control IOP. Prostaglandin
analogues are generally not recommended since there is
compromised access to the uveoscleral route. In addition, anti-
inflammatory agents such as topical steroid drops and
cycloplegic agents may be indicated to control any inflammation
and pain.
85. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Surgical Management of IOP
• Occasionally, although the angle is open, it may not
be possible to control IOP on medical management
alone. Surgical glaucoma intervention involving
filtering surgery, drainage implants, and/or
cyclodestructive procedures may be necessary.
The majority of patients with NVG eventually need
surgical intervention to control elevated IOP. In one
review, 80% of patients, if followed long enough,
needed glaucoma surgery for elevated IOP,
regardless of prior treatment .
86. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Filtering Surgery
• Filtering surgery is relatively effective in controlling elevated IOP
associated with NVG, but is at risk for failure due to severe
ocular inflammation. Results from two studies involving early
trabeculectomy with mitomycin C (MMC) have shown
successful IOP control of 53% at 13 months50 and 66.7% at 28
months.51 Another study in which trabeculectomy with MMC
was performed on eyes with active NVG secondary to PDR
showed success rates of 67% at 1 year and 61.8% after 2–3
years
87. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Mitomycin MMC soaked sponges are
used for intraoperative application
88. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
(M) Subconjunctival application of
mitomycin C.
• (M1) Antimetabolites are
especially important on filter
revisions where there is
increased tendency for
scarring. Notice the pledget is
pushed posteriorly to the
premade subconjunctival
pocket
89. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
(M) Subconjunctival application of
mitomycin C.
• M2) This drawing shows the typical
placement pattern for the sponges,
three in this case. The authors prefer
this placement pattern for fornix or
limbal filters. Currently, the pledgets
are placed posteriorly in order to
encourage flow away from the limbus.
Excessive flow directly over the fistula
is more likely to cause the bleb to
become pale and avascular. The dose
is 0.4 mg/mL for 4 minutes for NVG.
When performing a combined cataract
and trabeculectomy, one may
consider increasing the MMC
exposure time and/or concentration.
After the MMC is removed, the area is
profusely irrigated.
90. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Filtering Surgery
• The success rate has improved with performing adequate PRP
prior to surgery . When IVB was given preoperatively to eyes
that subsequently underwent trabeculectomy with MMC,
patients experienced decreased hyphema and increased
surgical success. At six months, 95% of IVB eyes achieved
complete success, whereas in the trabeculectomy with MMC
group only 50% achieved complete success and 75% had
qualified success, meaning they still required topical and/or oral
medications to control IOP.
91. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Drainage Implants
• Aqueous tube shunt implants have some success in the
treatment of refractory NVG, especially in situations where
conventional filtering surgery has failed.57,58 Many
practitioners prefer using glaucoma drainage implants (GDIs)
because they are less dependent on control of intraocular
inflammation and failure of the filtering bleb. Although the initial
response to Ahmed valve and Molteno implants is relatively
good, the long-term outcome is poor.
92. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
AGV contains a valve mechanism which must be
primed prior to insertion.
93. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Drainage Implants
• Young patients with poor preoperative visual acuity are at risk of
surgical failure. NVG itself is a risk factor for Ahmed valve
failure and worse visual prognosis.61 Use of adjunct IVB with
aqueous shunt implants has been shown to be successful. In a
study that included 56 eyes that received IVB and PRP for
NVG, those that required subsequent incisional surgery were
less inflamed and had lower intraoperative and post-operative
hemorrhage.62 This study also confirmed previous findings that
most patients with NVG, if followed long enough, require
surgical in
94. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Cyclodestructive Procedures
• Cyclodestruction to reduce production of aqueous
humor can be achieved with photocoagulation or
cryotherapy. Long-term results of noncontact
neodymium : yttrium–aluminum–garnet
cyclophotocoagulation in neovascular glaucoma
showed success rates of 65%, 49.8%, and 34.8% at
1-, 3-, and 6-year follow-up, respectively. Contact
transscleral diode cyclophotocoagulation is
effective in lowering IOP in eyes with neovascular
glaucoma.
95. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
Cyclodestructive Procedures
• However these procedures are not without risk,
including hypotony, phithisis, and vision loss.
Currently, a standardized cyclophotocoagulation
protocol in NVG has not yet been established.
Although the IOP can often be controlled, visual
outcomes are typically very poor, with the rate of
long-term visual loss in patients who have NVG
approaching nearly 50%.
96. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
TREATMENT OF LATE STAGES OF
NEOVASCULAR GLAUCOMA
• If the eye no longer has visual potential, it is recommended to
initiate medical therapy to control IOP, including cycloplegic
agents, steroid drops for comfort, PRP if the media is clear and
IVB. If the media is cloudy, then panretinal cryotherapy and
cyclodestructive surgery to control IOP will likely be needed. In
a study of 70 patients with NVG resistant to medical and
surgical treatment that were treated with transconjunctival
cyclocryocoagulation, there was a significant decrease in IOP
and eye pain after 180 days.
97. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
TREATMENT OF LATE STAGES OF
NEOVASCULAR GLAUCOMA
• However, if the eye has no vision and medical
therapy is not controlling the pain and discomfort,
more aggressive action may be needed such as
performing retrobulbar alcohol injection,
evisceration, or enucleation.
98. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CONCLUSION
• CRVO is a sight-threatening disease with significant ocular
morbidity, including macular edema and ocular
neovascularization. Before the recent advent of
intravitreal pharmacotherapy in the management of CRVO,
standard of care was guided by results from the CVOS,
which recommended observation of macular edema and
retinal ischemia with management of neovascular
sequelae using PRP. In the absence of robust treatment
options for CRVO,50 other approaches, including the
administration of r-tPA, creation of CRA, and various
surgical interventions, had been reported with variable
success and often unacceptable adverse effects.
99. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CONCLUSION
• More recently, intravitreal corticosteroids and particularly
anti-VEGF agents have demonstrated impressive
improvements in macular edema, visual acuity, and even
neovascular complications with a favorable side-effect
profile. The use of ranibizumab (Lucentis) and a sustained-
release dexamethasone implant (Ozurdex) have been FDA-
approved for the treatment of CRVO. Intravitreal
pharmacotherapy has now replaced
observation as standard of care for
management of macular edema associated
with CRVO.
100. INTRODUCTION CLINICAL PICTURE DIAGNOSIS COMPLICATION TREATMENT
CRVO
CRVO WITH MACULAR ODEMA
INVOLVING CENTRE OF RETINA
NO
OBSERVATION
YES
INTRAVITREAL AVASTIN .
STEROIDS MAY BE
CONSIDERED
FA
OBSERVATION FOR NVE & NVD & NVI
ESP IF CNP AREA MORE THAN 10 DD AREANO NVE
NVD, NVI
NVE,NVD OR NVI PRESENT
VITREOUS HGE & NVG
PRP + ARC
NO GRID LASER