Lens-Induced Granulomatous Endophthalmitis

Definition: Lens-induced granulomatous endophthalmitis is also known as phacoanaphylactic endophthalmitis, phacoantigentic and phacoallergic endophthalmitis. A granulomatous reaction to lens fibers that may appear zonal occurs in the setting of trauma and lens capsule rupture.

Incidence/ Prevalence: Very little good data exist on the exact incidence of this disease (see clinical findings).
Etiology: About 80% of cases are related to trauma, including surgical operations. Retained cortical fragments in the capsular bag after cataract operations have been reported to produce this disorder. (Ref 1). Occasionally presumed spontaneous rupture may be the culprit. Experimental studies, immunofluorescence and immunoperoxidase techniques, suggest that the inflammation is mediated by IgG.
Clinical Findings: Less than 5% of cases are diagnosed correctly clinically. The time of injury varied from 2 days to 59 years in one series (Ref 2). However, most sources state that it may occur as soon as 24 hours after surgery. Numerous anterior chamber cells, flare, keratic precipitates, posterior synechiae are often clinical findings. In the clincial photograph the lens is acutely ruptured and lens material (red arrow) rests adjacent to the cornea with pigment and a cellular anterior chamber infiltrate. The choroid is more often involved than clinically realized (Ref 2).

Histopathology: Histologically, lens-induced granulomatous endophthalmitis classically is described as a central nidus of degenerating lens material surrounded by concentric layers of inflammatory cells (zonal granuloma). Multinucleated giant cells (arrow 1) and neutrophils(arrow 2) may be present within the inner layer adjacent to the degenerating lens material. In the photo below multinucleated giant cells (arrow 4) are associated with the central lens fibers. There is usually evidence of lens rupture (arrows 3); the lens capsule is disrupted here. Lymphocytes and histiocytes may make up the intermediate mantle of cells. In chronic cases, there may be fibrosis surrounding the histiocytes (top of photograph).

Cytologic preparations show numerous histiocytes (black arrows) in proximity of degenerate lens material.
Treatment: Cycloplegics, corticosteroids and prompt removal of the lens are the usual therapeutic modalities.
Prognosis: With prompt lens removal the prognosis is largely dependent on other traumatic injuries. However, there may be associated sympathetic ophthalmitis.

References:

1. J Cataract Refract Surg. 2007;33:921-2.

2. Int Ophthalmol. 1991;15:271-9.

Mittendorf's dot

Definition: Mittendorf’s dot, also called the hyaloid body, is the embryologic remnant of the hyaloid artery as it joins the tunica vasculosa lentis.
Incidence/Prevalence: Mittendorf’s dot is present in normal eyes. It may be associated with posterior lenticonus.
Etiology: Mittendorf's dot represents the remains of the anterior end of the hyaloid artery.
Clinical Findings: On ophthalmoscopy Mittendorf’s dot may be visible as a black/gray axial or slightly nasal paraxial dot at the posterior apex of the lens. By slit lamp microscopy, Mittendorf’s dot is white. Attached one may find a thread-like structure, the remains of the anterior end of the hyaloid artery. The fibrous tissue of the fetal vasculature may extend through a gap in the lens and produce a posterior polar cataract. Progression may occur in the latter instance but is otherwise unusual.
Pathology: The hyaloid vascular system regresses usually by about 7 months. In the figure of this very premature infant, the tunical vasculosa lentis surrounds the lens (arrows 1) and is contiguous with the hyaloid vascular system (arrow 2). Notice the glial sheath of the hyaloid artery (arrow 3). Mittendorf's dot is evident as a white opacity on the posterior surface of the lens in an axial location of this adult autopsy eye (arrow 4).
Treatment: No treatment is generally necessary.

Posterior Lenticonus

Definition: Posterior lenticonus is a developmental anomaly of the lens in which the posterior portion of the lens bulges outward in a cone-shape.
Incidence/Prevalence: Posterior lenticonus is much more common than anterior lenticonus. Sporadic and inherited cases have been described, particularly X-linked and autosomal dominant inheritance patterns. Inherited cases are more common than sporadic cases.
Etiology: Associations include microcornea, anterior lentiplanus, glycinuria and Duane’s syndrome. [Ref 1] Although Alport’s syndrome is mostly associated with anterior lenticonus, simultaneous anterior and posterior lenticonus have been described in Alport’s syndrome.[Ref 2] It has been written that the abrupt thinning in the posterior capsule at the point of the lenticonus is the cause of the bulge on the basis of mechanical issues. This dogma of course does not adequately explain the inheritance patterns or associations! The association with Mittendorf's dot is particularly provocative.
Clinical Findings: Posterior lenticonus may be present at birth or develop in the following months. Amblyopia may be present. Posterior lenticonus may occur as an isolated ocular finding. There is a slight female predominance. Posterior lenticonus most commonly is unilateral but may be bilateral. There may be a high degree of astigmatism. Retinoscopy will show a distorted myopic reflex. Oblique lighting with the slit lamp is helpful to see the cone shape. With progression the cone and surrounding lamellae may opacify.
Gross and Histopathology: Histologic reports feature a thin posterior lens capsule. There is one report of an associated posterior subcapsular cataract. In the photograph (arrow 1) a rounded bulging of the posterior capsule is seen. This might be better termed lentiglobus because it is not truly cone shaped.
Treatment: If visually significant (opacified) or if amblyopia is present, lens removal is indicated. An anterior capsulorhexis with clear lens removal by aspiration and IOL placement within the capsular bag is the usual treatment. Often removal of the lens will restore vision. [Ref 3]
References
1. Surv Ophthalmol. 2003 Mar-Apr;48(2):125-44.
2. Indian J Ophthalmol. 2005 Sep;53(3):212-3.
3. J Cataract Refract Surg. 2006 Feb;32(2):261-3.

Marfan's Syndrome- Lens Displacement

Definition: Marfan's syndrome is a disorder of connective tissue with ocular, musculoskeletal, and cardiovascular manifestations.
Incidence/Prevalence: the most common cause of lens dislocation from a genetic mutation. The incidence is about 0.7/100,000 live births. The prevalence is 7-17/100,000 population.
Etiology: Marfan's syndrome is an autosomal dominant disorder caused by mutations in the fibrillin gene on chromosome 15. Fibrillin is a glycoprotein that is a major component in elastic tissue and is important in lens zonules. 50-80 percent of patients with Marfan’s syndrome have ectopia lentis.
Clinical Findings: Lens dislocation upward or superortemporally is the most common manifestation of ectopia lentis due to inferior zonule compromise. However, a 360 degree compromised lens zonule is possible in which case the lens floats in the posterior chamber.
Histopathology: The lens is usually displaced upward or in a superotemporal direction, and axial myopia is often present. In the accompanying images the lens is displaced upward because of inferior zonular compromise. The inferior border of the lens is concave in areas of zonular dehiscence (arrows #1 in gross photo). The displacement superiorly is evident by the increased distance between the lens and iris inferiorly (arrow #3 below) and their near apposition superiorly. The lens may bulge posteriorly (arrow #4 in microscopic photo). Sections generally show some morphologically normal appearing zonular fibrils that are decreased in number, and others that are short and in disarray. Associated findings include iris hypoplasia with transillumination defects and numerous iridociliary processes (arrows 2).
Treatment: When visual symptoms cannot be corrected medically, lens removal with trans-scleral or iris fixation may produce acceptable results. Sulcus placement may be difficult especially if there are numeorus enlarged cilio-iridal processes that bridge the ciliary sulcus and block the placement of a haptic.

Cortical Cataract

Definition: An opacity in the cortex of the lens, for which the key histologic criterion is the presence of globular degeneration.
Incidence/Prevalence: It is a common form of cataract and usually cortical changes are found accompanying nuclear sclerosis
Etiology: The eosinophilic globules are aggregates of lens crystallins.
Clinical Findings: Symptoms include glare while driving and, if the cataract is axial, a decrease in vision particularly with reading. Degenerative changes in the lens cortex may take on various appearances; spokes, fissures, lamellar separations, dot and wedge shaped opacities, rosettes and even a sunflower appearance have been described. With progression, the cortex may become mature and the nucleus floats within the bag. If the cortical material escapes from the lens capsule and produces wrinkles in the capsule, the lens is said to be hypermature.
Histopathology: The hallmark of the cortical cataract is globular degeneration. The process starts with alterations in cellular morphology with swelling and aggregation of protein. The lens cell membranes eventually break down releasing globules. Morgagnian globules consist of eosinophilic collections of protein (aggregates of lens crystallins) of various sizes that have lost cell membranes. Slits that appear as a result of cortical cataract usually contain eosinophilic material. This distinguishes cataract from artifactual separation of fibers during sectioning. As slits coalesce to form larger clefts, the cataract manifests spoke-like or wedge-shaped opacities.

Treatment: Surgical removal of the cataract generally restores vision.

Nuclear Sclerosis Cataract

Definition: An opacity in the nucleus of the lens, for which the key histologic criterion is melding or homogenization of lens fiber cells.
Incidence/Prevalence: It is the most common form of cataract and is especially common in older individuals. Subject prevalence for nuclear lens changes is about 3 fold higher than for posterior subcapsular opacities (Reference 1).
Etiology: There are many associations with nuclear cataract. The biochemical changes involve aggregation of lens crystallins as a predominant feature.
Clinical Findings: Symptoms include decreased vision and glare. The patients may experience progressive myopia as the refractive power of the lens accompanies the increased size of the cataractous lens. As the yellow color of the lens increases the patients may notice a subjective difference in their evaluation of colors (this is often referred to as the blue period for artists). Presumably photo-oxidation and the chromophore content accounts for the yellow to brown pigmentation.
Gross: The opacity may appear yellow to brown and loses transparency. In the photograph of a yellow to brunescent nuclear cataract one can appreciate the well defined nature of the nucleus (delimited by the arrows 1). The color varies but the brown pigment near the upper arrow is quite evident. The lens becomes more rigid and difficult to remove surgically as was the case for this lens.
Histopathology: Sections usually show a subtle melding of nuclear fiber cells that gives a homogenous eosinophilic appearance. The lens cells lose their concentric laminations. In the photomicrograph the lens fibers appear to be one mass of pink (arrow 2). The cleft (arrow 3) is an artifact of histologic sectioning. The cells generally do not undergo lysis and the lens cell membranes are generally preserved. The changes are often missed by the uniformed microscopist.
Treatment: Surgical removal of the cataract generally restores vision.
References:
Ophthalmic Epidemiol. 1997;4;195-206.

Anterior Subcapsular Cataract

Definition: An opacity in the lens positioned just posterior to the anterior lens capsule and is characterized by the proliferation of anterior lens epithelial cells.
Incidence/Prevalence: Anterior subcapsular cataract is less common than nuclear, cortical, or posterior subcapsular cataract. The subject prevalence for anterior subcapsular opacities is about 1/5 that of posterior subcapsular opacities (Reference 1).
Etiology: There are many associations with anterior subcapsular cataracts including inflammation, trauma, mitotics, amiodarone and atopic dermatitis. In animal models anterior subcapsular cataract has been produced with alkali burns. Some investigators suggest an epithelial to mesenchymal transition in these cells.
Clinical Findings: A focal star-shaped or irregular opacity beneath the anterior capsule as seen with a slit beam.
Histopathology: Sections usually show a multilayer of spindled epithelial cells beneath the lens capsule. In the photomicrograph the posterior pigmented layer of the iris is visible (black arrow 1). Previous posterior synechiae to the lens capsule is evidenced by the brown pigment deposition from the iris (black arrow 2). The multilayered lens epithelium is visible (white arrow 3 in figure) and to the left one can see that it is contiguous with a single layer of the normally present anterior lens epithelium. The photomicrograph at higher magnification shows the anterior subcapsular cateract at higher magnifcation, white arrow (the image below has been inverted). Sometimes the anterior lens capsule may be retracted and form slight protrusions.
Treatment: Surgical removal of the cataract generally restores vision.

References:

1. Ophthalmic Epidemiol. 1997;4;195-206.

Posterior Subcapsular Cataract

Definition: An opacity in the lens positioned just anterior to the posterior lens capsule and characterized by the posterior migration of lens epithelial cells from the lens bow.
Incidence/Prevalence: Posterior subcapsular cataract may be the most common abnormality involving the lens epithelium.
Etiology: The lens is composed largely of crystallins which aggregate in cataract formation. There are many associations with posterior subcapsular cataracts including chronic vitreal inflammation, ionizing radiation, trauma and prolonged use of corticosteroids.
Clinical Findings: Younger individuals may be affected and the symptoms include complaints of glare at night with bright headlights or poor vision with accommodation. Near vision may often be more affected than distance vision. Usually the earliest sign is a focal dot-like area on the posterior capsule or a reflective sheen. With progression, translucent opacities appear (the swollen Wedl cells) on the posterior capsule that have been likened to a “cloth of gold” or “fish eggs”. Posterior capsular cataract is associated with cortical degeneration and nuclear sclerosis.
Gross: An opacity that is central and irregular is the most frequent finding (arrow 1). Tangential lighting with transillumination will reveal that the opacity lies adjacent to the posterior lens capsule. Because cataracts are usually associated with other lens changes, careful examination will often reveal spokes or other cortical changes (arrow 2).
Histopathology: Normally, the posterior capsule is devoid of epithelium. The presence of nucleated lens epithelial cells (arrow 3) anterior to the posterior capsule (arrow 4) is the key histologic criterion for posterior subcapsular cataract. Posterior subcapsular cataract begins with presumed proliferation and posterior migration of epithelial cells from the lens bow. These cells, also known as bladder or Wedl cells may enlarge five or six fold. However, they do not always appear swollen in sections.
Treatment: Surgical removal of the cataract generally restores vision. In children medicated with steroids, posterior subcapsular cataract may be abated when the steroids are stopped.