Retinal Vein Occlusions

1
Retinal Vein Occlusions
2
Morphology

• CRVO
• BRVO
• Hemispheric VO
• Hemicentral VO
• Papillophlebitis
• Macular BRVO

3
CENTRAL RETINAL VEIN OCCLUSION

• The actual mechanisms producing the clinical
  picture of central retinal vein occlusion may be
  roughly divided into those conditions that
  produce a physical blockage at the level of the
  lamina cribrosa, and those conditions in which
  hemodynamic factors result in an obstruction to
  the flow of blood. These mechanisms probably
  coexist in many patients with central VO.

"Blood and thunder" appearance of a central
retinal vein occlusion.
4
PATHOLOGY

• Histopathologic evaluation of eyes removed
  because of a central retinal vein occlusion
  demonstrates an occlusion at or just behind the
  level of the lamina cribrosa.
• At this location, there are certain anatomic
  factors that predispose the central retinal vein
  to occlusion. First, the lumina of the central
  retinal artery and central retinal vein are
  narrower than they are in the orbital optic
  nerve, and the vessels are bound by a common
  adventitial sheath.

5
Anatomical Studies

• Green studied 29 eyes that were enucleated 6
  hours to 10 years after occlusion. As a result of
  this study, they hypothesized that the flow of
  blood through the central retinal vein becomes
  increasingly turbulent as the vein progressively
  narrows at the lamina cribrosa, where it also may
  be further impinged upon by arteriosclerosis of
  the adjacent central retinal artery. This
  turbulence damages the endothelium in the
  retrolaminar vein, which exposes collagen and
  initiates platelet aggregation and thrombosis.
• Their studies show the evolution of this
  thrombus. Initially, the thrombus adheres where
  the endothelium has been severely damaged.

6
Doppler Studies

• Recently, color Doppler ultrasound imaging has
  been used to examine the blood flow in the orbit,
  including the optic nerve head, and has been used
  to examine patients with central retinal vein
  occlusion.
• As might be expected, the venous velocity in the
  eye of a patient with central retinal vein
  occlusion is markedly reduced compared either
  with the unaffected eye or to control eyes.
• There is evidence, however, that the central
  retinal artery blood flow is also impaired in
  eyes with acute central retinal vein occlusion.
• In addition, vascular resistance is slightly
  higher in the ophthalmic artery and short
  posterior ciliary arteries of both the involved
  and the clinically healthy fellow eye of patients
  with central retinal vein occlusion compared with
  control eyes.
• There is also a trend toward higher vascular
  resistance of the central retinal artery in the
  clinically healthy eyes of patients with central
  retinal vein occlusion compared with control eyes.

7
Risk Factors

• An increased risk of central retinal vein
  occlusion was found in patients with systemic
  hypertension, diabetes mellitus, and open-angle
  glaucoma the risk of central vein occlusion was
  decreased for patients with increasing levels of
  physical activity and increasing levels of
  alcohol consumption.
• For women, the risk decreased with the use of
  postmenopausal estrogen and increased with a
  higher erythrocyte sedimentation rate.

The Eye Disease Case-Control Study Group Risk
factors for central retinal vein occlusion. Arch
Ophthalmol 114545, 1996
8
Risk Factors for Central Retinal Vein Occlusion
9
Investigations

• All patients with central retinal vein occlusion
  should have a comprehensive ophthalmic
  evaluation, including an appropriate evaluation
  for glaucoma. In addition, they should be
  referred to their primary care physician for an
  evaluation of cardiovascular risk factors,
  including hypertension and diabetes

• GENERAL PRINCIPALS
• Maximise Recovery and Vision
• Prevent re-occlusion
• Detect associated systemic disease
• Detect / Prevent Glaucoma
• Protect other eye

10
Standard Investigations

• FBC, PV, ESR
• UE, Creatinine
• LFT, Protein Electrophoreseis
• Random Glucose, Lipid
• Urine analysis

11
Ophthalmic Investigations

• FFA
• CDI (Color doppler )
• Carotid disease-Using digital subtraction
  angiography, Brown and associates studied 37
  patients with central retinal vein occlusion
  they found that significant ipsilateral stenosis
  (greater than 50) was not higher in these
  patients compared with historically matched
  controls. They did find, however, that patients
  with ischemic central retinal vein occlusion had
  a higher incidence of overall carotid
  atherosclerotic obstruction (ipsilateral and
  contralateral) than patients with nonischemic
  central retinal vein occlusion

12
Thrombophilic Screen ( less than 50 years )

•  
• Clotting screen
• Protein C,S defficiency
• Elevated factor V
• Actviated protein C resistance
• Factor V Leiden a major risk factor in females
  (Five percent of European population)
• Dysfibrogenaemia (1/3000)
• Prothrombin G20210A
• Antiphopholipid antibodies

13
Ischemic Central Retinal Vein Occlusion

• Patients with an ischemic pattern are usually
  aware of a sudden, painless decrease in visual
  acuity. Vision ranges from 20/400 to hand
  movements. The onset, however, is generally not
  as rapid or the visual loss as extensive as in
  central retinal artery occlusion. Exceptional
  cases have been noted in which patients with an
  acute onset had reasonably good vision and yet
  demonstrated a picture of ischemic central
  retinal vein occlusion. Patients with ischemic
  occlusion have an average age of 68.5 years.

14
Nonischemic Central Retinal Vein Occlusion

• Nonischemic central retinal vein occlusion is a
  much milder and more variable disease in
  appearance, symptoms, and course compared with
  ischemic central retinal vein occlusion. Patients
  with nonischemic central retinal vein occlusion
  are an average of 5 years younger (average age,
  63 years) than those with ischemic vein occlusion

15
Confluent hemorrhages are the most prominent
ophthalmoscopic feature of an acute ischemic
central retinal vein occlusion These hemorrhages
occur in a wide variety of shapes and sizes they
are usually concentrated in the posterior pole,
but may be seen throughout the retina.
Hemorrhages in the superficial retina may be so
prominent about the posterior pole that the
underlying retina is obscured. Many hemorrhages
are flame shaped, reflecting the orientation of
the nerve fibers. Dot and punctate hemorrhages
are interspersed and indicate involvement of the
deeper retinal layers. Bleeding may be extensive,
erupting through the internal limiting membrane
to form a preretinal hemorrhage or extending into
the vitreous. Small dot hemorrhages may be seen
either isolated or clustered around small
venules. The entire venous tree is tortuous,
engorged, dilated, and dark. The retina is
edematous, particularly in the posterior pole
some of this edema may obscure portions of the
retinal vessels. Cotton-wool patches (soft
exudates) are often present. The disc margin is
blurred or obscured, and the precapillary
arterioles appear engorged. Splinter hemorrhages
and edema are present on the disc surface and
extend into the surrounding retina. The
physiologic cup is filled, and the venous pulse
is absent. The arterioles, often overlooked
because of the other more striking pathologic
features, are frequently narrowed. Sometimes in
central retinal vein occlusion of acute onset,
the fundus picture is less dramatic, and all of
the findings previously discussed may be present,
but to a lesser degree. Vision depends on extent
of macular involvement.
Ophthalmoscopic features
16
Angiography

• The intravenous fluorescein angiogram pattern of
  an ischemic central retinal vein occlusion is
  usually characterized by a delayed filling time
  of the venous tree of the retina, capillary and
  venous dilation, and extensive leaking of
  fluorescein into the retina, particularly in the
  macular area and in the area adjacent to the
  larger venous trunks and capillary nonperfusion
  may not be noted at the time of initial
  occlusion, but are usually manifest shortly
  thereafter. Late-phase photographs show patchy
  extravascular areas of fluorescence and staining
  of the retinal veins. The intravenous fluorescein
  angiogram pattern of an ischemic central retinal
  vein occlusion is usually characterized by a
  delayed filling time of the venous tree of the
  retina, capillary and venous dilation, and
  extensive leaking of fluorescein into the retina,
  particularly in the macular area and in the area
  adjacent to the larger venous trunks and
  capillary nonperfusion
• Microaneurysms may not be noted at the time of
  initial occlusion, but are usually manifest
  shortly thereafter.
• Late-phase photographs show patchy extravascular
  areas of fluorescence and staining of the retinal
  veins. Fluorescence in the macula indicates
  capillary leakage and edema this not only may
  account for much of the initial visual loss in
  the acute phase, but may eventually result in
  permanent structural changes.

17
Classifying ischaemia

• The amount of nonperfusion or ischemia is
  determined by inspecting the fluorescein
  angiography negative under magnification. The
  photographer inspects not only the central 30 or
  45, but as much of the peripheral retina as
  possible.
• Another method has been to classify eyes with
  less than 10 disc diameters of perfusion on
  fluorescein angiography as perfused or
  nonischemic, and eyes with 10 or more areas of
  nonperfusion as nonperfused or ischemic.

18
Macular Oedema

• Fluorescence in the macula indicates capillary
  leakage and edema this not only may account for
  much of the initial visual loss in the acute
  phase, but may eventually result in permanent
  structural changes.

19
Prognosis CRVO

• The prognosis for ischemic central retinal vein
  occlusion is generally poor because of decreased
  visual acuity and neovascularization. Visual loss
  occurs because of macular edema, capillary
  nonperfusion, overlying hemorrhage (either
  retinal or vitreal), or a combination of all of
  these. Retinal edema usually gradually subsides
  except in the macula, where it may persist for
  many months or years. Macular holes or cysts may
  form.

20
Neovascularization

• The most serious complication of central retinal
  vein occlusion is neovascularization.
• Neovascularization elsewhere (NVE) occurs less
  frequently than neovascularization of the iris
  (NVI), and usually only in ischemic occlusions.
• The low incidence of retinal surface
  neovascularization in ischemic central retinal
  vein occlusion is thought to be due to the
  destruction of endothelial cells, which provide
  the source for endothelial proliferation and
  neovascularization.

21
Percentage of Ocular Neovascularization in Venous
Occlusion
22
Neovascularization of the Iris.

• Neovascularization of the iris and frequently
  neovascular glaucoma occurs in approximately
  86to 25 of all central retinal vein occlusions
  and generally only in those eyes that exhibit an
  ischemic pattern of occlusion.
• Magargal and co-workers have shown that the
  incidence of neovascularization increases
  dramatically above approximately 50 capillary
  nonperfusion. The incidence of anterior segment
  neovascularization in nonischemic central retinal
  vein occlusion is approximately 1, compared with
  approximately 35 to 45 for ischemic central
  retinal vein occlusion.
• Neovascularization of the iris or angle is
  significantly correlated with the extent of
  capillary nonperfusion on the fluorescein
  angiogram.
• Rubeosis developed in 80 to 86 of the eyes with
  severe nonperfusion of three to four quadrants of
  the posterior pole or the periphery, but in only
  3 to 9 of those with less capillary
  nonperfusion.

23
Neovascularization of the Iris

• Neovascularization of the iris may develop as
  early as 2 weeks after central retinal vein
  occlusion or as late as 2½1/2 years
  Neovascularization of the iris will develop in
  almost all patients within the first year, but
  usually in the first 3 months.89 Symptomatically,
  patients complain of tearing, irritation, pain,
  and further blurring of vision as the intraocular
  pressure in the affected eye begins to rise. The
  pain may become excruciating. The cornea is hazy
  and the pupil dilated, and a network of fine
  vessels is seen over the surface of the iris
  (rubeosis iridis) on slit-lamp examination. By
  the time gonioscopy reveals extension of this
  neovascular membrane into the trabecular network
  and throughout the angle, the intraocular
  pressure is usually markedly elevated. The angle
  is initially open, but later in the disease,
  peripheral anterior synechiae develop and the
  angle may become irreversibly closed, resulting
  in neovascular glaucoma. Large, extremely
  irritating bullae may form on the surface of the
  cornea and then break down. Dense cataracts
  eventually form, obscuring the fundus.

24
HEMICENTRAL AND HEMISPHERIC RETINAL VEIN
OCCLUSION

• The terms hemicentral retinal vein occlusion and
  hemispheric retinal vein occlusion refer to eyes
  in which approximately half of the venous outflow
  from the retina, either the superior or the
  inferior, has been occluded. In approximately 20
  of eyes, the branch retinal veins draining the
  superior and inferior halves of the retina enter
  the lamina cribrosa separately before joining to
  form a single central retinal vein.
• Hemicentral retinal vein occlusion is an
  occlusion of one of these dual trunks of the
  central retinal vein within the nerve.
  Hemispheric retinal vein occlusion is an
  occlusion involving the venous drainage from
  approximately half of the retina, either the
  superior or the inferior retina

25
Hemispheric retinal vein occlusions

• In some eyes, the nasal retina is not drained by
  a separate vein, but by a branch of either the
  superior or the inferior temporal vein. It is the
  occlusion of one of these veins draining both the
  nasal retina and the superior or inferior retina
  near the optic disc that accounts for the
  majority of hemispheric retinal vein occlusions.
• The treatment and classification are similar to
  that of branch retinal vein occlusion.

26
BRANCH RETINAL VEIN OCCLUSION
PATHOLOGY Leber was probably the first
investigator to note the connection between
branch retinal vein occlusion and the
arteriovenous intersection. Koyanagi found that
the majority (77.7) of his cases of temporal
vein occlusion involved the superior retina. He
attributed this to the preponderance of
arteriovenous crossings in this region compared
with other quadrants.Others later confirmed this
anatomic observation, noting that branch retinal
vein occlusion always occurs at an arteriovenous
intersection.Both fluorescein angiography1and
histopathologic examination confirm that most
occlusions occur at an arteriovenous crossing and
that the few that do not are in the vicinity of a
retinal artery. Histologically, where the vein
and artery cross, they share a common adventitial
sheath, and the venous lumen may be diminished by
as much as a third at this crossing.
27
Morphology

• The clinical picture of branch retinal vein
  occlusion is retinal hemorrhages that are
  segmental in distribution.
• The apex of the obstructed tributary vein almost
  always lies at an arteriovenous crossing. Usually
  some degree of pathologic arteriovenous nicking
  is present.
• The occlusion is commonly located one or two disc
  diameters away from the optic disc. However, the
  occlusion may lie at a point near the disc edge
  or, less frequently, may involve one of the
  smaller, more peripheral tertiary or macular
  branches.

28
Risk Factors for Branch Retinal Vein Occlusion

• Systemic hypertension
• History of cardiovascular disease
• Increased body mass index at 20 years of
  age cholesterol
• History of glaucoma
• High serum levels of a2-globulin

29
Management of BRVO

• Branch vein obstruction is often associated with
  pre-existing vascular disease. Evaluation for
  systemic abnormalities, in particular
  hypertension, should be performed. Exclusion of
  diabetes, hyperlipidaemia, hyperviscosity/coagulat
  ion states, antiphospholipid syndrome, or any
  other predisposing condition should be performed.
  Regular review is required until the haemorrhages
  clear so that the most suitable treatment option
  can be achieved. Approximately one third to one
  half of patients with BRVO have recovery of
  visual acuity to 20/40, or better, without
  therapy.

30
An important complication of branch retinal vein
occlusion is neovascularization

• Neovascularization of the iris and neovascular
  glaucoma are uncommon and occur in only
  approximately 1 of affected eyes.
• More commonly, neovascularization of the disc
  occurs in approximately 10 of eyes, and
  neovascularization elsewhere occurs in
  approximately 20 of eyes. Generally, retinal
  neovascularization occurs within the retinal area
  served by the occluded vessel, but it has been
  reported to occur outside in presumably normal
  retina.
• Vitreous hemorrhage due to neovascularization
  occurs in approximately half of the eyes with
  neovascularization.Butner and McPherson239 found
  that 11.3 of spontaneous vitreous hemorrhages
  were due to a branch retinal vein occlusion, an
  incidence second only to proliferative diabetic
  retinopathy as a cause of vitreous hemorrhage.
• Oyakawa and co-workers found that in 38.3 of
  eyes undergoing a vitrectomy for a nondiabetic
  vitreous hemorrhage, the hemorrhaging was due to
  a branch retinal vein occlusion.

31
Branch Vein Occlusion Study Group Vitreous
Hemorrhage

• Of patients with ischemic vein occlusion who were
  treated before neovascularization occurred, 12
  developed a subsequent vitreous hemorrhage,
  whereas only 9 of ischemic eyes treated after
  neovascularization occurred developed a vitreous
  hemorrhage. Although the study was not designed
  to determine the optimal time for treatment, the
  data suggest (but do not prove) that there may be
  no advantage to treatment before the development
  of neovascularization. The study was not able to
  draw conclusions about the effect of
  photocoagulation on the prevention of visual
  loss.

32
Branch Vein Occlusion Study Group- Macular Oedema

• Can photocoagulation improve visual acuity in
  eyes with macular edema reducing vision to 20/40
  or worse?
• Eyes with branch vein occlusion occurring 3 to 18
  months earlier with 20/40 vision or worse because
  of macular edema (but not hemorrhage in the fovea
  or foveal capillary nonperfusion) were treated
  with the argon laser in a "grid" pattern in the
  area of capillary leakage.
• The treatment did not extend closer to the fovea
  than the avascular zone and did not extend
  outside the peripheral arcade. At the 3-year
  follow-up, there was a statistically significant
  improvement in the visual acuity of treated eyes
  compared with untreated eyes.

33
MACULAR BRANCH RETINAL VEIN OCCLUSION

• An occlusion limited to a small venous tributary
  draining a section of the macula and located
  between the superior and inferior temporal
  arcades is considered a subgroup of branch
  retinal vein occlusion.Most patients with macular
  branch vein occlusion complain of blurring or
  distortion of vision. Superior macular vein
  occlusions are more common than inferior macular
  vein occlusions, and some degree of macular edema
  is present in approximately 85 of these eyes.
• Although small areas of capillary nonperfusion
  are present in approximately 20 of eyes,
  neovascularization is not seen. This type of
  macular vein occlusion can be remarkably subtle
  at times. Joffe and associates pointed out that
  clues such as small collateral channels and
  microaneurysms often suggest the diagnosis.
  Treatment of macular edema in macular vein
  occlusion by photocoagulation is identical to the
  treatment of other branch retinal vein occlusion.

34
Macular Oedema- FFA
35
PAPILLOPHLEBITIS

• In 1961, Lyle and Wybar described six young,
  healthy patients with a unilateral, relatively
  benign condition characterized by mild blurring
  of vision, essentially normal visual acuity,
  dilated and tortuous retinal vessels, a varying
  amount of retinal hemorrhage, and optic disc
  edema
• All six patients improved spontaneously, but were
  left with sheathing of retinal vessels and the
  formation of vessels on the optic disc. Lyle and
  Wybar called this condition "retinal vasculitis"
  and believed it to be due to a central retinal
  vein occlusion secondary to an inflammatory
  vasculitis of the venous system.
• Lonn and Hoyt agreed with this etiology, but
  felt that "papillophlebitis" was a more
  appropriate descriptive term. Hart and
  co-workers, however, pointed out that an
  inflammatory etiology for this disease is
  tenuous, and no well-documented cases have been
  studied histopathologically.

36
Investigations and therapy

• GENERAL PRINCIPALS
• Maximise Recovery and Vision
• Prevent re-occlusion
• Detect any associated systemic disease
• Detect / Prevent Glaucoma
• Protect other eye

37
General Therapy

• Avoid oral contraceptives
• Aspirin
• Treat hypercholesterolemia and hypertension
• Lower IOP
• Anticoagulants if required
• If vision drops consider re-occlusion.

38
Panretinal photocoagulation- Summary

• Panretinal photocoagulation has been recommended
  for the treatment of neovascularisation secondary
  to CRVO's. There is currently debate regarding
  the timing of this therapy. Whether delayed
  intervention (after the development of iris new
  vessels) offers as good an outcome as early laser
  treatment(at the time of neovascularisation of
  the retina alone) needs to be shown. Grid therapy
  for macular oedema in CRVO has not been shown to
  improve visual acuity.

39
Central Retinal Vein Occlusion Study Group -
Photocoagulation

• Hayreh and associates conducted a prospective but
  nonrandomized study of panretinal
  photocoagulation in ischemic central retinal vein
  occlusion. They found no statistically
  significant difference between the treated and
  untreated groups in the incidence of angle
  neovascularization, neovascular glaucoma, retinal
  or optic nerve neovascularization, vitreous
  hemorrhage, or visual acuity. The only
  significant finding was that fewer patients in
  the treated group had neovascularization of the
  iris compared with nontreated controls, but only
  if the panretinal photocoagulation was applied
  within the first 3 months after the onset of
  central retinal vein occlusion and panretinal
  photocoagulation resulted in a significant loss
  of the peripheral field.
• Once neovascularization in the anterior segment
  is detected, panretinal photocoagulation should
  be instituted promptly. This will often result in
  regression of the iris vessels and prevent
  complete angle closure this is also true in
  patients with some increase in intraocular
  pressure but in whom the angle is not occluded
  for 360.

40
Central Retinal Vein Occlusion Study Group-
Macular Oedema

• The Central Retinal Vein Occlusion Study Group
  performed a randomized, prospective clinical
  trial on the effect of macular grid
  photocoagulation compared with no treatment on
  eyes with 20/50 or worse visual acuity due to
  macular edema with no capillary nonperfusion on
  fluorescein angiography.
• Although grid photocoagulation lessens macular
  edema both angiographically and clinically, there
  was no difference in visual acuity between the
  treated and untreated patients. For treated
  patients, there was a trend toward decreased
  visual acuity in patients older than 60 years and
  visual improvement in patients younger than this
  this effect was not seen in untreated patients.
• Although this study suggests a possible benefit
  to visual acuity in younger patients with macular
  edema who are treated compared with untreated
  controls, the number of patients in this subgroup
  is too small for a statistically valid comparison
  of treated versus untreated eyes.

41
Chorioretinal anastomosis in patients with
nonischemic central retinal vein occlusion.

• McAllister and Constablereported a surgical
  technique to create a chorioretinal anastomosis
  in patients with nonischemic central retinal vein
  occlusion. Their current technique is to rupture
  Bruch's membrane first in an area adjacent to the
  edge of a vein located at least three disc
  diameters from the optic disc with the argon
  laser they then use a YAG laser to create a
  small opening in the sidewall of the adjacent
  vein.
• In their study there was an average of 2.1
  attempts to create an anastomosis, which was
  successful in only 42 of the patients in the
  first series171 and 67 of patients in the second
  series.172 In the first series, ischemic central
  vein occlusion did not develop in any of the
  patients in whom a successful anastomosis was
  produced, but it did develop in 31 of patients
  in whom such an anastomosis could not be
  created.171 It should be noted, however, that
  this is not a control group, and they have not
  reported on a controlled clinical trial of this
  procedure. All the patients with a successful
  anastomosis had an improvement in final visual
  acuity compared with pretreatment visual acuity.
  In the group of patients with an unsuccessful
  anastomosis, 38 had an improvement in visual
  acuity, 44 had a worse visual acuity, and 19
  had no change.
• There were some minor complications, such as
  vitreous and retinal hemorrhages, that tended to
  clear fairly well. However, there were some major
  complications, including a major fibrovascular
  proliferation at 14 of the sites where surgery
  was attempted.This complication can lead to
  serious, nonclearing vitreous hemorrhages and/or
  traction retinal detachment and may require a
  vitrectomy for treatment.
• Lacking a controlled clinical trial for this new
  treatment, there is no way to know whether laser
  chorioretinal anastomosis is more effective for
  nonischemic central retinal vein than no
  treatment.

42
Neovascular Glaucoma

• Once developed, neovascular glaucoma responds
  poorly to any type of treatment. Cycloplegics,
  topical pressure-lowering agents, carbonic
  anhydrase inhibitors, and corticosteroids, though
  failing to lower the intraocular pressure
  significantly, may make the patient more
  comfortable.
• Panretinal photocoagulation often cannot be
  applied in cases of advanced neovascular glaucoma
  in which the angle has been substantially
  occluded and the cornea may be too cloudy to
  allow treatment.
• Trans-scleral cyclocryotherapy or trans-scleral
  laser cyclodestruction, sometimes combined with
  360 of trans-scleral panretinal cryoablation,has
  also been used to preserve the globe.
• In some cases where visibility is poor and the
  angle is closed, we have had some success in the
  last few years combining pars plana vitrectomy
  and endophotocoagulation with a drainage implant

43
Contact Us

• Author John G. O'Shea MD
• Illustrations Robert Harvey FRCSEd (from
  Practical Ophthalmology, 2002 Palmtrees
  Publishing)
• Rob Harvey
• E-mail Address rob_harvey_at_msn.com
• Correspondence
• Birmingham and Midland Eye Centre, Dudley
  Rd, Birmingham B18 7QH, U.K