History
A 74-year-old woman developed neovascular glaucoma after a central retinal vein occlusion. The eye was
treated with laser photocoagulation of the ciliary body but subsequently enucleated.
Diagnosis
| | | |
| 1. | History of central retinal vein occlusion |
| (a) | Iris neovascularization |
| (i) | secondary angle closure |
| (ii) | optic atrophy |
| (b) | Optic disc neovascularization |
| (c) | Cataract |
| 2. | Laser photocoagulation of the ciliary apparatus |
| (a) | Vitreous organization |
| (b) | Funnel-shaped retinal detachment, tractional |
| (i) | retinal degeneration |
| (ii) | pre-retinal membrane of glial origin |
| (iii) | sub-retinal membrane of RPE origin |
| 3. | Uveitis, posterior, chronic, non-granulomatous, mild |
Histopathology
Apart from a fibrovascular pannus in the peripheral anterior stroma the cornea is essentially normal. The
trabecular meshwork is sclerosed and the angle is closed by peripheral anterior synechiae. There is a
neovascular membrane on the anterior surface of the iris. Degenerative changes, including calcification,
are seen within the lens cortex and subcapsular epithelial cells have migrated posteriorly. There is
hyalinization of the ciliary muscle and, in the posterior pars plicata on either side, the ciliary
epithelium is disrupted with fibrovascular ingrowth into the vitreous, consistent with previous
photocoagulation. Some of the vessels in the ingrowth are thin-walled but others have thick walls and are
quite large in diameter. The ingrowth is continuous with a thick fibrovascular membrane behind the lens
that has caused tenting of the peripheral retina. The detached retina is fixed and shows cystic
degeneration, disorganization and gliosis. Ganglion cells are reduced in number. Anterior to the retina
there is a thin membrane containing flattened spindle cells. Hemorrhage is noted anterior to, within and
beneath the retina. Also beneath the retina is a thick fibrovascular membrane associated with exudate,
cholesterol clefts and multinucleated giant cells. The retinal pigment epithelium (RPE) is focally
hyperplastic and shows considerable vacuolation. Both the retinal and posterior choroidal vessels are
sclerotic. Within the posterior uvea small collections of lymphocytes are present but granulomata are not
identified. The optic nerve head is slightly cupped with foamy macrophages in the pre-laminar zone and a
few small new vessels. Lymphocytes are noted around the central retinal vessels but previous occlusion
cannot be confirmed. The optic nerve is mildly atrophic.
Immunoperoxidase studies reveal strong GFAP-positivity of the internal limiting membrane and the pre-retinal
membrane, supporting a glial origin. The cells of the retrolental fibrovascular membrane express vimentin.
The cells of the subretinal fibrous membrane express vimentin and cytokeratin, consistent with an origin
from RPE.
Discussion
Retinal detachment (RD), defined as the separation of the neurosensory retina (NSR) from the RPE, occurs in
two forms:
Rhegmatogenous: a retinal break allows vitreous fluid to seep beneath the retina;
Non-rhegmatogenous: fluid or abnormal tissue accumulates beneath the intact NSR.
Retinal breaks are associated with cataract surgery, myopia, trauma and peripheral retinal degeneration but
not all breaks lead to RD and the condition of the vitreous is important. Non-rhegmatogenous RDs may be
exudative or tractional, in which fibrous or fibrovascular tissue pulls the NSR away from the RPE (see
Table). Eyes with exudative detachments may be received as surgical specimens but rhegmatogenous RDs are
usually seen after treatment failure, when the eye may have become phthisical or when a secondary
proliferative vitreoretinopathy (PVR) has supervened. Once the retina is detached the photoreceptor
elements, deprived of their blood supply, begin to degenerate and before the advent of modern surgical
techniques rhegmatogenous RD almost always resulted in blindness. Nowadays successful reattachment can be
achieved in 95% of cases and, if carried out promptly, may lead to satisfactory visual recovery as the
photoreceptors regenerate over several months. The basic principles of surgery are to close the retinal
break by approximating the sclera, choroid and RPE to the NSR ("buckling") and to create adhesion of the NSR
and RPE by drainage of subretinal fluid, tamponade and cryotherapy.1
During histological processing of an eye the NSR may shrink considerably and separate from the RPE. Such an
artefactual separation has three distinguishing features:
- absence of subretinal fluid
- photoreceptor elements are relatively intact
- pigment granules from the RPE are seen at the tips of the photoreceptor outer segments.
A true long-standing RD is characterized by:
- The presence of subretinal fluid
(although this may occasionally be lost during processing).
- Degeneration of photoreceptors
Loss of the inner and outer segments is complete and the number of
nuclei in the outer nuclear layer is markedly reduced. Photoreceptor death has been shown in both human and
experimental RD to occur via apoptosis.2-4
- Edema of the NSR
This results in small cystic spaces in the outer plexiform layer. After several
months of detachment macrocysts may occasionally (1% of cases clinically) be identified.5
- Proliferation of retinal glial cells
- Proliferation of RPE cells
At the margin of the detachment this may result in a clinically recognisable
pigmented demarcation line. RPE proliferation may be accompanied by the formation of prominent "papillary"
drusen.6,7 RPE proliferation
and fibrous tissue deposition in a plaque at the ora serrata is referred to as Ringschwiele.
- Proliferation of fibrovascular tissue (PVR)
This may occur on both the inner and outer surfaces of the
retina. Shortening and folding of the retina may produce a "funnel" of retina attached only at the ora
serrata and the optic nerve head.
- Hyalinization of choriocapillaris
Some of these changes may be seen in eyes following successful reattachment surgery, particularly epiretinal
membranes (76%) and some degree of photoreceptor atrophy (27%).8 Animal studies of morphological
recovery following reattachment surgery indicate that, even if the reattached retina looks normal
histologically, ultrastructural changes in the photoreceptor/RPE interface are usually recognizable.9
Such changes may be focal and not significant with respect to overall visual acuity; they are, however, more
marked in eyes with long periods of detachment (i.e. >1 month) in which visual recovery is poorer.9
Optic Atrophy
This is the end stage of any progressive degeneration or disease affecting the retina or optic nerve and is
characterised by the irreversible loss of axons. Optic atrophy may be classified as:
Descending: the primary lesion is either intracranial or in the retrobulbar nerve and the atrophy
"descends" to the eye, e.g., demyelinating disease, raised intracranial pressure.
Ascending: the primary lesion is either intraretinal or in the optic nerve head and the atrophy "ascends"
to the brain, e.g., retinal detachment.
The histopathological features of the atrophic optic nerve are:
- loss of myelin, and with time, axons;
- disturbance of parallel columns of glial nuclei;
- gliosis;
- widening of the subdural space; thickening of the pial septa.
Optic atrophy of whatever cause ultimately leads to disappearance of retinal ganglion cells and also axons
of the optic nerve, chiasm and optic tract as far as the lateral geniculate nucleus (LGN) of the thalamus.
These axons normally form synapses with the neurons of the LGN which project to the occipital cortex through
the optic radiation.
The LGN is composed of 6 cellular laminae separated by thin, cell-free zones. The ventral laminae (1,2)
contain large neurons and the dorsal laminae (3-6) smaller ones. Laminae 1,4 & 6 receive axons from the
contralateral, nasal retina and laminae 2,3 & 5 from the ipsilateral, temporal retina. Each lamina thus
contains a precise map of the contralateral hemifield and the six maps are stacked in vertical register.10
Retinal detachment in one eye will lead to optic atrophy and, by transsynaptic degeneration, produce
atrophy of layers 2,3 & 5 of the ipsilateral LGN and layers 1,4 & 6 of the contralateral LGN. This can be
demonstrated in post-mortem material by Nissl stains and, owing to the restricted nature of the afferents to
the LGN, constitutes the best example of central transsynaptic degeneration in human pathology.
