Progressive retinal degeneration in the Siberian husky dog

Ophthalmic Pathology Primer

This is a beginner's lesson in ophthalmic pathology, aimed at general pathologists or ophthalmology residents who are just starting their residency.

It is intended to give the essentials on how to prepare an eye for histologic evaluation and some normal microscopic anatomy critical for interpretation of the abnormal. It is basically a Web publication of the lecture I give to general pathology residents.

This is primarily a pictorial guide. A textual outline of general principles of ophthalmic pathology is in another document.

Removal of the eye

This should be done as quickly as possible, without compromising patient safety if the patient is under anesthesia or immediately after euthanasia. Care should be taken not to incise the globe during the enucleation. Although the optic nerve should not be cut from the globe at this point, adnexal tissue unnecessary for making a diagnosis should be gently trimmed from the globe before fixation in order to improve preservation of tissues.

The eye should be placed in fixative as soon as practical after removal. Many of the tissues, the retina in particular, are very sensitive to anoxia and the longer you wait to fix the eye, the greater will be the artifacts, making interpretation difficult.

If you are dealing with a necropsy situation, and the eyes cannot be removed and fixed immediately after death, it is better to leave the eyes undisturbed in the body until fixation can be done. Compared with removing the eyes and, for example, refrigerating them until fixation, leaving them in the body until fixation can be done results in less artifacts being introduced.

Fixing an eye for histologic evaluation

Light microscopy (routine microscopy)

The globe should never be opened nor injected with fixative. To do so can introduce substantial changes that may interfere with interpretation. Simple immersion fixation is adequate.

Davidson's solution or Bouin's solution is the routine fixative used. Either of these provides adequate preservation of tissues and should be used for all globes. The disadvantage of Bouin's is the presence of picric acid which can create additional safety problems if it becomes dehydrated.

Formalin should not be used on globes if this can be avoided because it does not provide adequate preservation of the retina in particular. It should be limited to adnexal tissue. One exception to this is if you want to do something like enzymatic digestion for flat preparation of retinal blood vessels.

Although Zenker's acetic acid solution provides excellent preservation of all ocular tissues for routine light microscopy, its use cannot be justified because of its mercury content.

Electron microscopy

Glutaraldehyde is the best fixative if you need to fix small pieces of tissue and do not need to retain anatomical integrity with respect to spatial relationships between various ocular structures. For example, if you are only interested in the corneal endothelium, immediately removing the eye the cornea can be excised and immersed into the fixative, giving exceptional preservation of the tissue. The same is true for the retina or any of the intraocular epithelial tissues.

Other good fixatives for electron microscopy include mixtures of glutaraldehyde and paraformaldehyde or Karnovsky's solution.

Labeling of containers

Whether you send the tissue to another laboratory or prepare it for embedding yourself, it is important to carefully mark the containers and cassettes with the side (left or right) in order to minimize confusion later.

Gross examination and cutting in of tissue for routine light microscopy

Principles

It is generally a good idea to measure the globe to determine anterior-posterior, vertical (in the parasagittal plane) and horizontal dimensions. These data are helpful in deciding if the eye is other than normal size. Prior to doing this, most of the peribulbar (adnexal) tissue should be examined and trimmed and discarded if not important to the evaluation.

If sufficient (at least 2 mm) optic nerve is attached to the globe, it should be should be removed close to, but not flush with, the globe. The piece removed can provide cross sections which give a better idea of the breadth of lesions than would longitudinal sections alone. In glaucomatous globes, however, there may be substantial optic disk cupping so that severing the nerve too close to the globe can in effect perforate it. If glaucoma is suspected, therefore, at least 1 mm of nerve should be left attached.

If the globe has been fixed in aldehydes, it can be transilluminated to observe internal shadowing by unsuspected masses, etc.

The portion of the globe that is submitted for routine examination is termed the pupillary-optic disk portion (or the P-O). This allows examination of almost all the tissues of the eye and provides a standardized anatomical representation so that comparisons can be made with other specimens for that species. This may have to be sacrificed if lesions are known to be in regions necessitating some other way of preparing the eye.

To get the P-O portion, you have to remove tissue to either side, going from anterior to posterior or vice versa. The portions removed are called calottes because they look like caps. The plane of your incision to remove the calottes depends primarily on the species in question.

s_2054_2.jpg In species which have a tapetum, such as the cat, dog (at left), some primates, and horse, the goal is to provide sections which include tapetal and nontapetal portions of the ocular fundus. This requires that the plane of section be parasagittal (vertical). The calottes, therefore, are medial and lateral.

s_3612_1.jpg In those primates who have maculas and foveas, the goal is to provide sections which include these structures. Because the macula, with the fovea in its middle, is located lateral to the optic disk, the plane of section must be horizontal. Therefore, the calottes that are removed are dorsal and ventral.

In all other species, such as birds, rabbits, reptiles, it is desirable to make the plane of section parasagittal in order to provide a standardized view. This is not always feasible in some species in which determining dorsal from ventral and so forth is a challenge in an eye removed from the body.

If there is a particular lesion or a suspected neoplasm that would not likely be included in the P-O portion of the globe, the ideal way to deal with this is to submit separately the calotte in which the lesion resides. Less desirably, you could also make your plane of section other than standard so that the P-O portion would include the lesion.

Determining plane of section

Where feasible, in order to adhere to the principles stated, you will need to determine dorsal from ventral by identifying external features.

s_1499_1.jpg In this dog globe (left), viewed from the front, the third eyelid (which should be left attached if convenient) provides information on anatomic position. It is located medially and the leading edge describes an arc extending roughly from dorsomedial to ventrolateral.

s_1172_1.jpgThe long posterior ciliary artery, seen in the side view at left, provides an important landmark for determining horizontal from vertical. It is located slightly above the level of the optic nerve and extends in a horizontal plane lateral and medial to the optic nerve. Make your cuts perpendicular to this when you want a P-O in the parasagittal plane (most eyes) and parallel with this for primates who have a macula and fovea.

Making the cuts

A sharp razor blade should be used. If appropriate, remove the optic nerve at this time. If you wait until you have opened the globe, it will be more difficult to do this.

After removal of the optic nerve, place the globe corneal end down on a paraffin block and position it so that you can draw the razor blade across the globe in a direction to and from your body. Hold it on one side with thumb and forefinger; enough pressure should be applied so that it will not rotate as you cut, but not enough that intraocular contents will extrude when the globe is opened. The cuts should be made several millimeters to either side of the optic nerve, in the plane appropriate for the species.

The first cut is usually easy and should be made on the side opposite to that being held. That is, the cut should be made so that you remove the presumptive calotte opposite to the one being held by your digits. Use to and fro steady sawing motions as you firmly press the razor blade against the globe. Once started, do not stop, but continue and apply greater pressure as you meet the resistance caused by the anterior ocular tissues (the edge of the lens or the inner aspect of the cornea and sclera). If you cannot get through these tissues in this manner, stop sawing and, with the blade in the incision, press firmly down on the blade to push it through the tissues until the blade enters the paraffin along its entire length.

Because the globe is now open, there is often little resistance to deformation when you start the second cut to isolate the P-O portion. Greater care is needed in order to get a good P-O portion that is not greatly distorted and can fit into a cassette easily. The next cut is made between where you are holding the globe and the optic nerve in order to remove the remaining presumptive calotte. As with the first cut, make sawing motions as you less firmly press down on the globe. With practice, you will be able to press down sufficient to cut tissue, but without bending it to the point it gets pushed away from you without being cut. Again, once the cut starts, do not stop, but continue as with the first cut until you either complete it or have to push the blade through.

Tissues to submit

The tissues to submit for paraffin embedding and sectioning should include:

Routine stains to request for paraffin embedded tissues

Hematoxylin and eosin should be done on all tissues.

For all globes, periodic acid-Schiff should be requested. This is important for demonstrating basement membranes (corneal epithelial, Descemet's membrane, lens capsule, internal limiting membrane of retina), photoreceptor outer segment matrix and various parasites.

Although not routinely done in a non-ophthalmic pathology lab, Luxol fast blue with cresyl echt-violet counterstain is an excellent method of demonstrating myelinated nerve fibers in the optic nerve. The Bodian stain is complementary and accentuates for axon cylinders in the optic nerve. These should be requested, if desired, for the globe and separate pieces of optic nerve if appropriate.

Reading the slides

There is no rule concerning this. However, because the eye is comprised of many tissues, it is best to develop a fixed routine so that no areas are missed. You might consider going from the front to the back.

Normal anatomy, age-specific variations and artifacts

It is critical that you thoroughly understand normal ocular anatomy, down to the cell level, if you expect to make reliable diagnoses. Although the following will show you some of the highlights or will simply demonstrate normal anatomy through photomicrographs, this may not be sufficient. It is not intended to be a detailed lesson in ocular anatomy. You should have available to you literature which describes and illustrates ocular anatomy, including the differences between species. Understanding the latter is fundamental to proper interpretation.

As much as was feasible, I have used photomicrographs of routine preparations, rather than those of exceptional quality and exquisite detail. This was done so that the appearance of tissues would more closely resemble what you might see or expect for routine microscopy.

For many of the illustrations that follow, left clicking the mouse over them will display the original magnification image from which they were taken. Generally, if the image has a border, it is linked to the original image for this function.

s_5471_1.jpg The illustration at left shows an ideal section of an entire globe. It was carefully cut and spread in the water bath and then properly floated onto a slide so that there was minimal tearing, folding and or the introduction of other artifactitious changes. You can use this as a reference point for visualizing the spatial relationship of various tissues.
Ocular anterior segment (normal)
s_4021_2.jpg The illustration at left shows a portion of the ocular anterior segment. Although cellular detail is not discernible, the spatial relationships of the various anterior structures should be clear.

The limbus is the junction between sclera and cornea and is the line of demarcation between the more eosinophilic sclera and the less eosinophilic cornea.

The chambers of the eye include:

  • The anterior chamber is the space delineated by the posterior surface of the cornea, the anterior surface of the iris and the anterior surface of the lens.

  • The posterior chamber is the space delineated by the posterior surface of the iris, the inner surface of the ciliary body and the anterior surface of the lens from about the equator to the pupil.

  • The vitreous cavity is the largest space and is delineated by the inner surface of the retina, the posterior surface of the lens and the inner surface of the ciliary body.

Cornea (normal)
s_4015_1.jpg Normal cornea under relatively good conditions of fixation and preparation. Notice that there is considerable artifactitious tiny spaces. This cornea is of a young dog, hence the prominence of the keratocytes (cells in the stroma).
s_3829_1.jpg Normal cornea under relatively poor conditions of fixation and preparation. Notice that groups of collagen lamellae are widely separated by artifactitious spaces and the endothelium is prominently vacuolated.
s_5609_1.jpg Normal cornea under moderate conditions of fixation and preparation. Notice that groups of collagen lamellae are widely separated by artifactitious spaces. Notice also an acellular, subepithelial layer known as Bowman's layer is present; this is found in certain primates and some other non-domesticated species such as cetaceans.

Drainage angle (normal)
s_4020_1.jpg The photomicrograph at left shows the drainage angle under relatively good conditions of fixation and preparation. This angle is referred to as being 'open' because there is no collapse of the trabecular meshwork and there is access to it (presumed to be on either side of the pectinate ligament strand). This is of a young dog. Not all species have a pectinate ligament (monkeys, for example, do not) and even in those that do, a complete strand is not always in section.

Lens (normal)
s_0510_1.jpg Normal lens under relatively good conditions of fixation and preparation. The lens bow is from where new fibers are formed. The splitting of tissue and separation of capsule from cortex are common artifacts.
s_4680_1.jpg Normal lens cortex under relatively good conditions of fixation and preparation. The numerous splits in the tissue are common artifacts.
s_4666_1.jpg Normal lens cortex under relatively good conditions of fixation and preparation. The splits in the tissue with granular material within are artifacts in this case.
s_4683_1.jpg Normal lens cortex under relatively good conditions of fixation and preparation. The spaces in the tissue with granular material within are artifacts in this case.
Ocular posterior segment (normal)
s_4022_1.jpg The illustration at left shows a portion of the ocular posterior segment. Although cellular detail is not discernible, the spatial relationships of the various anterior structures should be clear.

s_1015_1.jpg Normal retina, cat, tapetal region, under relatively poor conditions of fixation and preparation. This is the typical appearance when formalin fixation is used: the sensory retina often separates from the epithelium, there are numerous inter- and intracellular spaces, and there is lack of cellular detail. The retinal epithelium is amelanotic over much of the tapetal region making it difficult to see in this preparation.
s_4229_2.jpg Normal retina, dog, tapetal region, under relatively good conditions of fixation and preparation. This is the typical appearance when Zenker's fixation is used; Bouin's solution provides a somewhat less desirable result, although superior to formalin. The retinal epithelium is amelanotic over much of the tapetal region. The outer and middle limiting 'membranes' are not membranes; they appear this way due to the linear arrangement of intercellular junctions (outer) or synapses (middle).
s_4230_2.jpg Normal retina, dog, nontapetal region, under relatively good conditions of fixation and preparation. This is the typical appearance when Zenker's fixation is used; Bouin's solution provides a somewhat less desirable result, although superior to formalin. The retinal epithelium is melanotic in this region (except in albinotic or subalbinotic individuals). The outer and middle limiting 'membranes' are not membranes; they appear this way due to the linear arrangement of intercellular junctions (outer) or synapses (middle). The nerve fiber layer is not prominent in this region.
s_4516_2.jpg Normal retina (immature), dog, tapetal region, under good conditions of fixation and preparation. This immature retina (late prenatal) demonstrates the temporal difference in maturation between inner (earlier) and outer (later) regions. Note that photoreceptor outer segments are non-existent and inner segments are barely detectable. The neuroblastic layer will differentiate into outer and inner nuclear layers. The tapetum is also immature at this age.
s_6015_2.jpg Normal retina (immature), dog, tapetal region, under good conditions of fixation and preparation. This immature retina (28 days postnatal) demonstrates the continued postnatal maturation of retina in altricial species such as the cat or dog; the process is not complete until about 7-8 weeks. Note that photoreceptor inner and outer segments are shorter than they will be when mature. The tapetum is also immature at this age.
s_5243_1.jpg Normal retina, cat, nontapetal region, under good conditions of fixation and preparation. It is not unusual to find cones or rods displaced to the photoreceptor inner and outer segment region; this is apparently part of the process of disposing of dead or dying cells, a natural process of attrition.
s_5240_1.jpg Normal retina, cat, nontapetal region, under good conditions of fixation and preparation. It is not unusual to find a few macrophages (phagocytes) amongst the photoreceptor inner and outer segments; this is apparently part of the process of disposing of dead or dying cells, a natural process of attrition.
s_4890_1.jpg Normal retina, monkey, under relatively good conditions of fixation and preparation. The macula is the ganglion cell and cone rich region of the retina in many primates. The fovea is devoid of most inner retinal layers and provides the most acute vision. Although birds and many other species may have a fovea, they usually do not show a macula (which just means a visible spot).
s_1167_1.jpg Peripheral cystoid retinal degeneration, dog, under relatively good conditions of fixation and preparation. This is an expected age-related finding in many species. It begins within the first few months of life. It can be substantial, as in this 19 year old dog, but does not appear to affect vision because of its peripheral nature.
s_2285_1.jpg Peripheral cystoid retinal degeneration, dog, under relatively good conditions of fixation and preparation. This is the histologic appearance of tissue similar to that seen in the gross specimen above. Compare this with the appearance of the ora serrata retinae in a young animal.
s_2944_1.jpg Normal retina, mouse, under good conditions of fixation and preparation. Mice and other small rodents have similar appearing retinas and have no tapetum. Although mice and rats have a well-vascularized retina, some rodents, like the degu, do not.
s_4217_1.jpg Normal retina, opossum, tapetal region, under good conditions of fixation and preparation. Opossums have a tapetum that is located within the cytoplasm of the retinal epithelium, resulting in extremely thick (around 150 µm thick) cells. This necessitates retinal vasculature extending down to the level of the external limiting membrane, something that would be considered highly abnormal in many other mammals.
s_4218_1.jpg Normal retina, opossum, nontapetal region, under good conditions of fixation and preparation. Notice the retinal epithelium is thinner here and has abundant melanin granules in the apical region (the side closer to the photoreceptor outer segments).
s_1240_1.jpg Normal retina, rabbit, peripapillary region, under moderate conditions of fixation and preparation. Notice the large retinal blood vessels are on the surface of the retina, with capillary extensions down into retinal tissue.
s_4841_1.jpg Normal retina, elephant, tapetal region, under fairly good conditions of fixation and preparation. It is much like horse retina.
s_2085_1.jpg Normal retina, pig, under fairly good conditions of fixation and preparation. Pigs have more cones and ganglion cells than many other domestic species.
s_7429_1.jpg Normal retina, finback whale, under relatively poor conditions of fixation and preparation.
s_3418_1.jpg Normal retina, tree kangaroo, under relatively good conditions of fixation and preparation. An unusual feature is the presence of oil droplets within the outer tip of the photoreceptor inner segments (more easily seen in the higher magnification image seen by left clicking on this image).
s_1010_1.jpg Normal retina, snake, under relatively poor conditions of fixation and preparation. There are relatively few photoreceptors and most of these are cones.
s_2574_1.jpg Normal retina, gecko, under very good conditions of fixation and preparation. There are relatively few photoreceptors and most of these are rods. The paraboloids are glycogen-rich membranous structures within the photoreceptor inner segments.
s_5140_1.jpg Normal retina, bird, under good conditions of fixation and preparation. Bird retina is avascular.
s_5142_1.jpg Normal optic disk region, bird, under good conditions of fixation and preparation. Unique to birds is the pecten, the vascular structure arising from the surface of the optic disk.
s_1225_1.jpg Normal optic disk region, hamster, under relatively good conditions of fixation and preparation. A unique feature of a few rodents and many reptiles is the presence of a conus papillaris, which is a melanotic, vascularized structure on the inner surface of the optic disk. It is similar to the pecten of birds.
s_0989_1.jpg Normal optic disk, snake, under relatively poor conditions of fixation and preparation. A unique feature of many reptiles and a few mammals is the presence of a conus papillaris, which is a melanotic, vascularized structure on the inner surface of the optic disk. It is similar to the pecten of birds.
s_2572_1.jpg Normal optic disk region, gecko, under very good conditions of fixation and preparation.

Pathologic changes

The following will illustrate some of the pathologic changes seen in specific ocular tissues. This is intended to show the cellular changes that indicate diseased tissue, not necessarily specific syndromes. Often, as in the retina or lens, deciding whether a particular finding is pathological may be the most challenging aspect of evaluation.

Pathologic changes common to virtually any tissue in the body will not be illustrated except where there are features that are specific to a particular ocular tissue.

Cornea (abnormal)
s_1669_1.jpg Corneal edema. Notice that although collagen lamellae are separated, this is not in otherwise normal groups and the spaces contain lightly staining material rather than the emptiness seen in artifactitious separation.

Lens (abnormal)
Determining what is artifact and what is pathologic in the lens is often difficult. Small, focal lesions seen clinically may not be in section. Vagaries of fixation and preparation often introduce changes that can easily be confused with cataractous ones. As a result, clinical evaluation of the living lens using biomicroscopy is often far more reliable than histologic evaluation if the changes are subtle or incipient. When the histologic findings are not unequivocal, the final interpretation should take into account the biomicroscopic findings. If a careful clinical exam had been done and the lens was normal, and you see histologic changes that could be artifactitious, it would probably be appropriate to conclude that the latter is true.
s_4652_1.jpg Cataractous lens under relatively good conditions of fixation and preparation. The unequivocal (not subject to artifact) cataractous changes include loss of the bow, proliferation of the epithelial cells without forming fibers at this site, aberrant attempts at fiber formation (the 'bladder cells', which are swollen presumptive lens fibers with retained nuclei) and posterior migration of epithelium under the lens capsule (no cells should be under the posterior part of the lens capsule).
s_1420_1.jpg Cataractous lens under relatively good conditions of fixation and preparation. The unequivocal (not subject to artifact) cataractous changes include aberrant attempts at fiber formation (the 'bladder cells', which are swollen presumptive lens fibers with retained nuclei) and posterior migration of epithelium under the lens capsule (no cells should be under the posterior part of the lens capsule). The vacuoles are almost certainly not artifactitious in this case, given their appearance and location amongst other pathologic changes.
s_2197_1.jpg Cataractous (incipient) lens under relatively good conditions of fixation and preparation. The unequivocal (not subject to artifact) cataractous changes are the retained nuclei in the subepithelial fibers; these fibers are mature and should have lost their nuclei. The fissures are artifacts of preparation.
s_4656_1.jpg Cataractous lens under relatively good conditions of fixation and preparation. The cataractous changes are the large zones of degenerated (granular) fibers in between ones that are almost normal. Although in general these regions appear similar to what was described as artifact in another section previously, the scope of the changes and knowledge about the clinical appearance of the lens were enough to conclude that they were pathological.
s_2286_1.jpg Cataractous lens under relatively good conditions of fixation and preparation. The unequivocal (not subject to artifact) cataractous change is the zone of epithelial proliferation (fibrous metaplasia). The fissures are artifacts of preparation.
s_4638_1.jpg Cataractous lens under relatively good conditions of fixation and preparation. The unequivocal (not subject to artifact) cataractous change is the thick zone of epithelial proliferation (fibrous metaplasia). The pockets of altered cortical material at the arrows is almost certainly real necrosis. The fissures are artifacts of preparation.
s_1609_1.jpg Cataractous lens under relatively good conditions of fixation and preparation. The unequivocal (not subject to artifact) cataractous changes include the folding of capsule indicating rupture, loss of cortex and degeneration and mineralization of remaining cortex.

Iris (abnormal)
s_4570_1.jpg Iris neovascularization. There is a pre-iridal fibrovascular membrane on the anterior surface of the iris; also known as rubeosis iridis.
s_4557_1.jpg Iris neovascularization. There is a pre-iridal fibrovascular membrane on the anterior surface of the iris; also known as rubeosis iridis.
s_5686_1.jpg Ectropion uvea. The pupillary border of the iris has been everted due to a pre-iridal fibrovascular membrane on the anterior surface of the iris. The bending of the iris sphincter muscle is helpful in differentiating this condition from a normal, but prominent pupillary ruff which extends anteriorly.
s_1676_1.jpg Entropion uvea. The pupillary border of the iris has been inverted due to fibrous tissue. There is a combination of a pre-iridal fibrovascular membrane and a fibrous membrane on the posterior surface. The bending of the iris sphincter muscle is diagnostic for entropion uvea in this case.

Retina (abnormal)
s_5492_1.jpg Retinal neovascularization. New blood vessels have developed from existing ones and grown outward into the vitreous cavity. The neovascularization in this dog was associated with the collie eye ocular maldevelopment syndrome.
s_4141_1.jpg Retinal separation. This section shows the difference in retinal structure in a region where the sensory retina is in situ versus where it has separated from the retinal epithelium. Notice that in the region of separation, the photoreceptor outer segments are degenerating and the retinal epithelial cells are rounded up and protruding inward. These changes provide unequivocal evidence of the separation being pathologic rather than artifactitious. The separation in this cat was due to choroidal vascular disease.
s_4899_1.jpg Rod-cone dysplasia. This is from a 6 week old Irish setter, demonstrating the lack of normal development of rods and cones. Although not all preparations will be this good, making interpretation easy, these are the key features that are unequivocal with respect to a diagnosis: 1) there is very little outer segment material, 2) the few inner segments remaining are diminutive and wider than normal, and 3) there is a reduction in the number of photoreceptor cell bodies (comprising the outer nuclear layer; because the thickness of this layer differs from one region to another, be sure to compare with a similar region in a normal retina). Notice also that the inner retinal layers are normal. Compare with similarly prepared normal retina of a dog of same age (although the latter is of the nontapetal region).
s_0380_1.jpg Photoreceptor dysplasia. This is from a 3 month old miniature schnauzer, demonstrating the lack of normal development of rods and cones, although the primary problem appears to be with the rods at this early age. Notice that there is very little outer segment material in general, a substantial loss of rods over cones, and a reduction in the number of photoreceptor cell bodies (comprising the outer nuclear layer). Notice also that the inner retinal layers are normal.
s_5935_1.jpg Rod-cone degeneration. This is from a 10 month old miniature poodle, demonstrating the degeneration of photoreceptors, after essentially normal development. Notice that in this region, which is near the optic disk, there is very little outer segment material in general, a substantial loss of rods and cones, and a reduction in the number of photoreceptor cell bodies (comprising the outer nuclear layer). Notice also that what can be seen of the inner retinal layers is normal. Degeneration is initially greater near the optic disk than more peripherally.
s_6165_1.jpg Rod-cone degeneration. This is from a 10 year old miniature poodle, demonstrating the extensive degeneration of photoreceptors at this late stage. Notice that in this region, which is near the optic disk, and at this age, outer segments and inner segments are almost absent and there is substantial reduction in the number of photoreceptor cell bodies (comprising the outer nuclear layer). Notice also that the inner retinal layers are normal.
s_0360_1.jpg Rod-cone degeneration. This is from a 5 year old golden retrieve, demonstrating the extensive loss of photoreceptors at this late stage. Notice that even though there are virtually no photoreceptors, the inner retinal layers are indistinguishable from normal, emphasizing the fact that this is a photoreceptor disease as opposed to a diffuse retinal disease.

Glaucoma
s_4562_1.jpg Angle closure. There is no access to the trabecular meshwork due to proliferation of fibrovascular tissue on the anterior surface of the iris (pre-iridal fibrovascular membrane or rubeosis iridis). This tissue is also adherent to the cornea and sclera (peripheral anterior synechia). Compare with normal angle.
s_0903_1.jpg Angle closure. The trabecular meshwork is obliterated and there is no access to it due to peripheral anterior synechia. Stretching of the globe has caused substantial distortion of normal anatomic relationships. Compare this angle with a normal angle.
s_4661_1.jpg Retinal degeneration. Typical of glaucoma, the primary changes are in the inner retinal layers, comprising loss of ganglion cells and their axons (nerve fiber layer) and diminution of the inner plexiform layer. Notice the increased prominence of Müller cell processes in the inner layers due to loss of surrounding tissue. Compare this retina with normal retina from the normal eye of this individual.
s_4644_1.jpg Retinal degeneration. Although the primary changes are in the inner retinal layers, photoreceptors are often also involved in chronic cases, such as in this dog. Frequently, the degenerative process is substantially less in the retina overlying the tapetum, as is seen here. Compare this with retina in the nontapetal region from the same eye of this individual. The sensory retina in this region is reduced to a gliotic membrane and the retinal epithelium is essentially absent.
s_4179_1.jpg Optic disk cupping. A combination of high pressure and loss of ganglion cell axons results in posterior displacement of the optic disk (cupping). True cupping always involves a degree of posterior displacement of the lamina cribrosa. Compare this cupped disk with a normal optic disk.
s_4702_1.jpg Optic nerve degeneration. This Bodian stained cross section shows mild to moderate loss of axon cylinders compared with similar preparation of a normal optic nerve.
s_7352_1.jpg Optic nerve degeneration. This Luxol fast blue stained cross section shows moderate loss of myelin compared with similar preparation of a normal optic nerve.
s_4650_1.jpg Rupture of Descemet's membrane (clinically known as Haab's striae). Between the ends of the ruptured membrane, there has been mild fibrous metaplasia of the corneal endothelium, which is not uncommon in this condition.

Neoplasia
s_1945_1.jpg Non-teratoid medulloepithelioma. These arise primarily from ciliary body epithelium or optic disk. Because the tissue resembles retina, they are often mistaken as retinoblastomas.
s_1947_1.jpg Non-teratoid medulloepithelioma. This part of the neoplasm in particular looks like dysplastic retina with regions neuroblastic in appearance or resembling "rosettes."
s_1950_1.jpg Non-teratoid medulloepithelioma. This part of the neoplasm in particular looks like neoplastic retina, showing a fleurette, which is a characteristic of retinoblastomas.
s_0518_1.jpg Teratoid medulloepithelioma. These arise primarily from ciliary body epithelium or optic disk. There can be many different tissue types because of the pluripotential nature of the derivative tissue. As with the non-teratoid type, because regions look like retina, these are misinterpreted as retinoblastomas.
s_0522_1.jpg Teratoid medulloepithelioma. This region appears like a neurogliomatous neoplasm.
s_0528_1.jpg Teratoid medulloepithelioma. This region appears like ependymal tissue.
s_0531_1.jpg Teratoid medulloepithelioma. This region has glandular tissue in the form of secretory ducts.
s_0533_1.jpg Teratoid medulloepithelioma. This region has cartilaginous differentiation.
Chediak-Higashi Syndrome
s_2941_1.jpg Aberrant melanosome formation, mouse. Compare with similar region of retina in normal mouse.

Calotte - to be correct, it is not a calotte until it is removed and assumes a cap shape