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The deposits of cornea guttata, which often precede Fuchs' endothelial dystrophy, represent a risk factor in patients undergoing intraocular surgery, rendering a cornea unsuitable for use as donor material. These corneal guttae clinically resemble subendothelial blebs that accompany various corneal and anterior segment inflammatory conditions so that confusion between the two groups is possible. In differentiating the two groups it is noted that (a) guttae are more elevated and usually appear in the relief mode; (b) the endothelial mosaic, if present, is usually relatively normal around the guttae; (c) both guttae and blebs may be contiguous and even confluent; (d) guttae are more regular and endothelial cells are often arranged regularly around them; (e) although small guttae may occur, if guttae are at all numerous, large ones are also usually present; and (f) inflammatory cells are rarely present in the relief mode with guttae but are always present with blebs associated with uveitis.

It is sometimes claimed that a relationship exists between Fuchs' dystrophy and angle closure glaucoma and that this is an indication for the simultaneous performance of keratoplasty and cataract extraction in patients with Fuchs' dystrophy. If such a relationship exists, then the anterior chamber depth in Fuchs' dystrophy should resemble that in angle closure glaucoma and a significant degree of cornea guttata might be expected to be common in angle closure glaucoma. In 88 patients with angle closure glaucoma we found that the anterior chamber depth was significantly shallower than in cornea guttata or Fuchs' dystrophy for acute (p < 0.001), chronic (p < 0.002) or incipient angle closure glaucoma (p < 0.001). Cornea guttata and Fuchs' dystrophy were very infrequent in these patients with angle closure, only two having cornea guttata and one Fuchs' dystrophy. These results do not support a relationship between angle closure glaucoma and Fuchs' dystrophy or cornea guttata and do not justify performing combined cataract surgery and keratoplasty in all cases of cornea guttata or Fuchs' dystrophy undergoing keratoplasty. Each case should be assessed on its merits and combined surgery should be reserved for patients shown to have a shallow anterior chamber or significant cataract.

Specular microscopy provides a level of magnification and differentiation of detail which approaches that of a histological examination, and has the advantage of being a noninvasive procedure. This makes specular microscopy useful not only in examining the corneal endothelium, but also in identifying deep corneal opacities, which fall into two broad groups: 1) exogenous materials deposited in the cornea; and 2) endogenous pathologic corneal changes. Exogenous materials in the cornea have a wide variety of appearances, including the typical appearance of caterpillar hairs, the multifaceted appearance of glass foreign bodies, the regular geometric appearance of cholesterol crystals and cigar-shaped myeloma crystals or the more irregular deposits of chlorpromazine. Endogenous changes include ghost vessels, larger striate corneal nerves, fasciculi of fine parallel lines in keratoconus, criss-cross irregularly running lines in resolved keratitis, and a shagreen or cellophane-like appearance suggesting thickening of Descemet's membrane. While some deep corneal opacities are easily diagnosed clinically, the nature of others may be difficult to determine and specular microscopy is a valuable aid in such cases.

Corneal oedema and bullous keratopathy may occur following intraocular surgery or arise spontaneously in nonguttate eyes. In some patients the fellow eye shows a relatively normal endothelial cell count with abnormal pleomorphism and polymegathism of the endothelial cells, while in others it shows a markedly lowered endothelial cell count with no evidence of corneal guttae. A survey of 17 such patients suggested the following classification. 1. Nonguttate corneal endothelial dystrophy with irregular endothelial cell morphology but a relatively normal endothelial cell count occurring following surgery (eight patients) or spontaneously (four patients). 2. Nonguttate corneal endothelial dystrophy with grossly reduced endothelial cell count occurring spontaneously (two patients). Three additional post-surgical patients showed a relatively normal endothelial cell count and only mild changes in the morphology of the corneal endothelium. These findings support the presence of a nonguttate corneal endothelial dystrophy in both the spontaneous and some of the post-surgical cases.

Although phacolytic glaucoma is well known and the clinical picture is well recognized, the nature of the polychromatic hyperrefringent granules is less well understood. A series of five cases was examined by specular microscopy, and the anterior chamber aspirate obtained at operation was subsequently examined by direct microscopy of the wet aspirate. Direct microscopy showed that the macrophages identified histologically in the aspirate corresponded to regular round cells about three times the size of an erythrocyte seen in the relief mode of specular microscopy. This finding aided in the interpretation of cellular deposits seen on specular microscopy. One hyperrefringent granule was seen on the posterior endothelium on specular microscopy, and results of subsequent examination of the aspirate showed this and the crystals in another patient to be morphologically identical with cholesterol crystals. The findings confirm that cholesterol crystals are present in the exudate in phacolytic glaucoma and are responsible for hyperrefringent granules.

Objectives: To provide a comprehensive description of the clinical presentations, cataract morphology, and molecular basis of hereditary hyperferritinemia-cataract syndrome (HHCS) in 4 Australian pedigrees and to estimate its prevalence. Methods: All known cases of HHCS in southeastern Australia were ascertained. Family members provided a medical history and underwent physical examination, lens photography, and venipuncture for measurement of serum ferritin levels and DNA extraction. Sequence analysis of the iron-responsive element of the ferritin light chain on chromosome 19q13.3-qter was performed. Results: We investigated 26 affected individuals from 5 Australian pedigrees. Two pedigrees with HHCS ascertained independently were subsequently found to form 1 large kindred carrying the mutation A40G. The minimum estimated prevalence of HHCS is 1/200 000. One pedigree had the mutation G32C. Among 2 smaller pedigrees studied, one carried a novel mutation (C39A), and the other was identified through the 2-year-old propositus with cataract but no positive family history. The latter case was shown to be due to a de novo mutation (G32U). All cataracts were highly distinctive in morphology, consisting of slowly progressive flecks, vacuoles, and distinctive crystalline deposits scattered predominantly in the lens cortex but also in the nucleus. Eight of 18 affected individuals examined have required cataract extraction to date. No other identified clinical manifestations of HHCS were delineated. Conclusions: Cataract morphology in HHCS is highly distinctive. Longitudinal observation demonstrated slow progression of the cataracts. This study highlights that, although HHCS is an autosomal dominant condition, the diagnosis should be considered even in sporadic cataract of typical morphology. Furthermore, individuals with unexplained hyperferritinemia should be referred for ophthalmological assessment, as the cataract may be asymptomatic but lead to a correct diagnosis of HHCS. Clinical Relevance: Progressive cataracts of highly distinctive morphology are an important feature of HHCS. Evaluation for this type of cataract may be of diagnostic value in patients with unexplained hyperferritinemia. Hereditary hyperferritinemia-cataract syndrome can be a cause of cataracts in pediatric patients even in the absence of any positive family history.

Two patients with deep corneal stromal opacities occurring after prolonged contact lens wear are described. The opacities were associated with folds or striae in Descemet's membrane which they overlay. Development of the opacities was associated with ocular discomfort, photophobia, reduced vision and a history of prolonged daily wearing times. Although the corneal endothelial cell counts were within the normal range, the count was reduced in the affected eye in the patient with the unilateral deep stromal opacity and there was mild polymegathism of the endothelial cells. It is possible that the long-term effects of subtle endothelial cell changes may cause a keratopathy with later scarring and opacification. Poor oxygen transmissibility, carbon dioxide build-up, or suction effects by the lens may all be aetiological factors. Early recognition and treatment, particularly with a better fitting lens of high oxygen transmissibility is important, as once developed the opacities regress only slowly and may result in permanent visual impairment.

The corneal endothelium was assessed following penetrating keratoplasty in a series of 50 patients and eight illustrative cases are described. Assessment disclosed a wide variation in the endothelial cell count and morphology following keratoplasty. In some patients the endothelial cell count was so low and the morphology so abnormal that long-term survival of the graft was doubtful. In cases with such a low count it is very doubtful, whether the graft will survive a secondary procedure such as cataract extraction or, intraocular lens implantation. Some donor material may carry corneal guttae and the use of such material should be avoided. If the material is good it will withstand inflammatory episodes including graft rejection if treatment is prompt and appropriate. Satisfactory material may be obtained from elderly donors while a young donor does not guarantee suitable material. It is desirable to assess the corneal endothelium of donor material carefully before use.

Subendothelial blebs were seen in cases of superficial keratopathy of varied etiology: superficial punctate keratopathy (42 patients); keratoconjunctivitis sicca (11 patients); epithelial basement membrane dystrophy (9 patients); mild superficial keratopathy due to exposure (9 patients), trichiasis (6 patients), or chemical contact (4 patients); and in contact-lens wearers (29 patients). The blebs were probably due to intercellular edema, separating endothelial cells from Descemet's membrane, and were reversible after resolution of the keratopathy. If the condition is chronic, changes in endothelial morphology may occur, with pleomorphism and polymegathism of the endothelial cells. These cases show that conditions which cause fine disruption of the corneal epithelium affect the integrity of the corneal endothelium. Recognition of resulting long-term changes may be important before intraocular surgery or if the cornea is to be used for grafting.

We have demonstrated the reversibility of corneal endothelial changes which accompany superficial keratopathy (superficial punctate keratitis, exposure keratopathy, chemical keratopathy and keratocon-juncitivits sicca). stromal keratitis and anterior uveitis (predominantly iridocyclitis). These changes include small subendothelial dark areas equal to or less than one cell in diameter and larger subendothelial dark areas up to two to four cells in diameter. These dark areas are similar but form two groups. The smaller ones may be due to oedema, some developing into larger dark areas, but it is also possible that smaller dark areas represent inflammatory cells or even local destruction of endothelial cells. The larger dark areas elevate the overlying endothelium. Either may be very numerous. They may be present together or separately. They become much less numerous and disappear with resolution or suppression of the acute keratitis or uveitis. The relief mode of corneal specular microscopy was used to distinguish these dark areas from other inflammatory and degenerative changes (such as fine inflammatory deposits. larger keratic precipitates, pigment deposits and guttatae at the level of the corneal endothelium).

Fluorescein angiography of the iris vasculature and specular microscopy of the corneal endothelium were used to examine two important anterior chamber tissues in cases of heterochromic cyclitis, classical chronic cyclitis and some cases of iridocyclitis. The 13 cases of heterochromic cyclitis and eight cases of classical chronic cyclitis all showed vascular hypoperfusion of the iris, except for two young females with heterochromia. In these cyclitic eyes there was pupillary leakage of dye and all but one young female with heterochromia showed evidence of microneovascularization of the iris. Most patients showed evidence of abnormalities of the corneal endothelium, but this was most marked in elderly patients with heterochromic cyclitis, probably due to the long duration of the condition. Six of the patients with chronic cyclitis had bilateral disease and five of these were elderly women with glaucoma and grey irides, the group being distinct enough to form a discrete clinical entity. Seventeen of the patients with chronic cyclitis were females with grey irides suggesting that this type of patient is more susceptible to cyclitis. Patients with acute iridocyclitis showed little abnormality on fluorescein angiography, while those with recurrent or chronic disease showed vascular hypoperfusion and microneovascularization suggesting that these changes in the iris contribute to the chronicity of the condition. It is suggested that hypoperfusion and microneovascularization of the iris and abnormal permeability are important factors in the production of chronic cyclitis, and that the integrity of the corneal endothelium is affected by these changes if they operate over a long period of time.

The ability of the cornea to maintain its transparency after surgery depends primarily upon the integrity of the corneal endothelium and in corneal grafting this is important for both donor and recipient eyes. The corneal endothelium may be significantly affected in various conditions of the anterior segment, especially if these exist over a considerable period of time. These conditions include superficial keratopathy, long-term contact lens wear, cornea guttata and low-grade anterior uveitis, especially chronic cyclitis which may be almost imperceptible clinically. The suitability of such corneas for use as donor material as well as the response of the eyes to anterior segment surgery can be assessed by specular microscopy and this may become even more important in the future as long-term contact lens wearers become more numerous in the community.

In order to differentiate clearly red blood cells and their relationship to the corneal endothelium, specular microscopy was performed in patients with hyphaema due to contusion injury. This enabled the clear identification of red blood cells as rounded, umbilicated or flattened spheroidal structures depending on whether they were seen side on or end on. They were seen best in the relief mode lying on the posterior endothelial surface and not infiltrating the corneal endothelium. It also disclosed the presence of subendothelial blebs one to three cells in diameter seen at the level of the corneal mosaic and not in the relief mode. These are probably due to mild oedema following the contusion injury and were distinct from the red blood cells. The corneal endothelial cell count and morphology were similar to that in the other eye when the changes resolved a week or so after the injury.

Deep corneal opacities due to posterior polymorphous dystrophy, especially if they are mild, are frequently confused with changes due to other corneal conditions. In a series of 64 patients with deep corneal opacities (14 with Descemet's tears, 8 with posterior polymorphous dystrophy, 12 with interstitial keratitis, and 30 with keratoconus), specular microscopy enabled the differentiation of deep corneal changes provided some degree of corneal clarity was retained. The parallel "rail track" borders of old Descemet's tears were characteristic and differed from the "snail tracks" seen in posterior polymorphous dystrophy, which also showed characteristic rounded vesicular or doughnut-like lesions in Descemet's membrane. The appearances in interstitial keratitis were varied with poor detail in most cases because of corneal opacity. However, fine opacities consistent with ghost vessels were seen in interstitial keratitis and a resolving case showed fine, intersecting straight lines different from the bundles of parallel fine vertical lines of deep corneal striae in keratoconus. Specular microscopy also enables an assessment of the corneal endothelium which is important if intraocular surgery is contemplated.

A medical photography unit can aid hospital infection control policies by documenting effects of disinfectants on hospital equipment and by its more customary role of preparation of teaching aids on the subject. Medical photography units can also be instrumental in spreading infection in hospital. Results of investigations into this are shown, together with suggestions for preventing this spread, and for minimising any risks to photographers.

The use of the specular microscope as a noninvasive in vivo method of identifying cholesterol crystals in two cases of crystalline corneal deposits is described. This illustrates the advantage of using the specular microscope under living conditions with a much higher magnification than is obtained with the slit lamp. Attention is drawn to the wider applications of this method.

A series of five cases is described in which superficial punctate keratopathy was associated with endothelial cell changes. The most striking change was the presence of dark areas or blebs, usually two to four cell diameters in extent. There was also distortion and crumpling of the corneal endothelium, mild pleomorphism and polymegathism of the endothelial cells, with a reduced cell count in some cases. These blebs have previously been reported in hard and soft contact lens wearers and are due to intercellular oedema with separation of endothelial cells from Descemet's membrane. Anoxia and interference with osmosis have been proposed as possible mechanisms for the production of these blebs, but our cases demonstrate that fine disruption of the corneal epithelium can affect the integrity of the corneal endothelium and may lead to significant damage over a long period of time.

We have demonstrated marked changes in the corneal endothelium in some groups of patients with ocular anterior segment disease including chronic cyclitis, both heterochromic and classical, pseudoexfoliation of the lens capsule, and anterior segment pigment dispersal syndrome. The most striking changes occurred in heterochromic cyclitis with reduced endothelial cell counts (p less than 0.01) and altered cellular morphology. In almost all eyes with cyclitis endothelial belbs were seen. In eyes with unilateral pseudoexfoliation of the lens capsule there was a lower endothelial cell count with pleomorphism and polymegathism, the changes being somewhat more marked with raised intraocular pressure (p less than 0.01). In anterior segment pigment dispersal syndrome there was an even smaller reduction in count (p less than 0.05) with mild changes in morphology. Factors producing endothelial cell changes included hypoperfusion of the iris with microneovascularization of the iris stroma, intercellular bleb formation with oedema of the corneal endothelium, and raised intraocular pressure. A normal iris circulation is important to the integrity of the corneal endothelium.

The use of specular microscopy is not confined to the corneal endothelial mosaic, but may be used at any level through the corneal stroma to the posterior endothelial surface. In the stroma the not very dense, irregularly rounded deposits of corneal dystrophies may be differentiated from the dense, geometric shapes of crystalline deposits. At the level of Descemet's membrane the fine parallel lines of tears in Descemet's are distinct from the multiple fine vertical deep stromal lines seen in advanced keratoconus. At the level of the endothelial mosaic the cells may be counted and their morphology examined, while blebs may also be seen in a wide variety of pathological conditions including superficial keratopathies, contact lens wearers, deep keratopathies, anterior uveitis and contusion injury. These blebs vary in size in different conditions and are often transient. They must be distinguished from guttae which are permanent and although an occasional finding in normal corneas are a constant feature of cornea gutatta and Fuchs' dystrophy. On the posterior endothelial surface the relief mode enables the examination of numerous deposits including red blood cells, white blood cells, keratitic precipitates, pigment granules and pseudoexfoliative KP. The morphology of these various findings is discussed.

Recent work has shown changes in the corneal endothelium accompanying corneal epithelial disease and anterior uveitis. It is important to differentiate these acute changes from other changes such as guttatae or corneal pigment deposition and to assess the magnitude of their effect upon the corneal endothelium. We have used specular microscopy to study changes in the corneal endothelium and Descemet's membrane and to study deposits on the back of the corneal endothelium and correlate them with changes in the endothelium by the use of conventional specular microscopy and by relief images which give a three dimensional view of the area concerned. This has particularly been applied to the conditions of superficial punctate keratopathy, keratoconjunctivitis sicca, corneal abrasions and exposure keratopathy, iritis and cyclitis, pseudoexfoliation of the lens capsule, anterior segment pigment dispersal syndrome, bullous keratopathy as well as corneal guttatae and pigment granules on the posterior cornea. Preendothelial lesions have been distinguished from endothelial and retrocorneal lesions by this technique aiding elucidation of the state of the endothelium. The changes which we noted occurred either at the level of Descemet's membrane (including formation of small rounded dark blebs less than one cell in diameter, larger blebs one to three cells in diameter, and guttatae, usually larger than the foregoing and sometimes very numerous), or at the level of the posterior endothelial surface (including small shiny nodular deposits, often numerous, due to pigment granules, and keratitic precipitates and inflammatory debris, the former usually large and the latter smaller, more irregular and sometimes very numerous). The differentiation and assessment of these various changes are discussed.

Changes on corneal endothelial specular microscopy were compared in 14 patients with cornea guttata, 4 patients with Fuchs' corneal dystrophy and 19 patients with various forms of bullous keratopathy. The patients with cornea guttata showed well marked guttae 1 to 6 endothelial cells in diameter in the endothelial mosaic and in the relief mode while the endothelial mosaic was usually otherwise within normal limits. In 2 patients with Fuchs' dystrophy the endothelium could be examined, showing gross guttae but a few areas of relatively normal endothelial cells. The unaffected eye of 3 other patients showed findings similar to cornea guttata, but with some reduction in endothelial cell count in 2 patients. The patients with bullous keratopathy fell into 2 groups, one with gross reduction in cell count in a markedly abnormal endothelial cell mosaic, the other a mixed group with moderate reduction in cell count and numerous guttae. Some miscellaneous cases included one of aphakic peripheral bullous keratopathy, one associated with cyclitis and aphakia and 2 with idiopathic non-surgical bullous keratopathy. We believe the corneal endothelium is not grossly abnormal away from the guttae in Fuchs' dystrophy, but the gross guttata formation determines the endothelial dysfunction.

Use of the relief mode of specular microscopy to differentiate corneal endothelial changes in anterior segment disease from retrocorneal deposits facilitates understanding of the nature of the endothelial changes. The retrocorneal deposits may be pigment granules or inflammatory deposits. The inflammatory deposits may be due to fibrin or WBCs, are more irregular than pigment, and may coalesce to form large, rounded, keratic precipitates. Pigment granules are smaller, denser, usually more regular and, although sometimes confluent, do not form keratic precipitates. Both are distinct from subendothelial blebs, both the smaller blebs up to one cell in diameter and larger blebs of two to three cells in diameter. These blebs are probably due to edema, disappear quickly on resolution of the pathologic process, and are evidence of stress to the endothelium, which shows significant change in morphology and fall in cell numbers when the blebs are of long-standing.