When is it appropriate to refer patients with Fuchs’ endothelial dystrophy (FED) for cataract surgery? In this article the characteristics of FED are explored along with the surgical approaches that can be taken when cataract develops in these patients.
Fuchs’ endothelial dystrophy (FED) is a progressive disease affecting the endothelium of the cornea, which can significantly affect vision, and can be concomitant in cataract patients. When assessing a cataract patient, either in general optometric practice or in a hospital cataract clinic, it is important to diagnose FED early to help in surgical planning and providing perioperative counselling to the patient regarding the risk of corneal oedema and possible corneal transplant soon after cataract surgery if corneal decompensation occurs. Perioperative counselling will improve the patient’s acceptance of the need for further surgery. Identifying the severity of FED prior to surgery is important as combined cataract and corneal procedures can be indicated in certain cases, whereas others may simply require a cataract procedure.1-3 This article will discuss FED and its detection, and the management options for these patients when cataract surgery is required.
Origins of cataract surgery complications with FED
FED was first described in 1910 by the Viennese ophthalmologist, Ernst Fuchs, who reported epithelial and stromal oedema in a group of 13 patients, which he described as ‘dystrophia epithelialis corneae.’4 These are now known to represent advanced stages of FED. A decade later Vogt identified drop-like endothelial changes in the cornea, using slit lamp biomicroscopy, which are now termed guttae.5 Later, Friedenwald and Friedenwald noted the evolution of guttae in the cornea of one patient to progress over several years to the characteristic features of Fuchs’ dystrophia epithelialis corneae, namely stromal and epithelial oedema, and identified guttae as an early sign of FED.6 In a report to the New York Ophthalmological Society in 1912, Knapp noted that some patients who underwent cataract surgery later manifested clinical signs of dystrophia epithelialis with stromal and epithelial oedema, as described by Fuchs;7 this is now known as pseudophakic bullous keratopathy (PBK), which is a complication of cataract surgery especially in patients with FED.
CharacteristicsThe early findings described above characterise the three-stage process of FED.3 The first stage is usually asymptomatic and involves development of excrescences of Descemet’s membrane. The excrescences, or guttae, generally begin centrally and then extend to include the peripheral cornea; this stage is most commonly seen in the third to fifth decades of life. As endothelial cells undergo apoptosis, the remaining cells stretch to cover the areas of the absent cells resulting in varied endothelial cell size (polymegathism) and varied cell morphology (pleomorphism).8 As the cells enlarge, many of them undergo apoptosis, and the reduction in the number of cells contributes to a loss of overall pump function, which is otherwise essential to maintain appropriate levels of hydration within the cornea. This process least to the second stage, stromal oedema, which arises from the ability of the endothelium to pump out fluid from the stroma resulting in symptoms of reduced vision. Epithelial oedema is a result of the anterior movement of aqueous and fluid in the stroma driven by intraocular pressure. As the disease progresses, there is increased accumulation of fluid and blisters and bullae develop which can result in pain as they burst, forming epithelial erosions.8 The advanced third stage of FED is characterised by sub-epithelial connective tissue scarring and peripheral corneal neovascularisation. Hence, FED is a disease of Descemet’s membrane and endothelial cells, while changes in the corneal stroma and epithelium are secondary to the endothelial dysfunction.
FED is a bilateral, slowly progressive, primary disorder of the corneal endothelium. It can be either sporadic or hereditary. In hereditary cases, the inheritance is demonstrated to be autosomal dominant with 30% of patients known to have a family history of the disease.9 It is more prevalent in women with a ratio as high as 4:1.9 The penetrance and disease expression can vary from family to family.
Endothelial cell density is highest at birth (6000 cells/mm2) and decreases in a non-linear fashion in the first couple of years due to rapid growth in the cornea. Thereafter, there is a linear loss and average cell density in an adult is 2400 cells/mm2.8,9
Endothelial cell density is a gauge of endothelial function, although it does not always correlate with corneal thickness. As endothelial cells apoptose due to attrition or trauma (as in cataract surgery) neighbouring cells migrate and enlarge to maintain the endothelial monolayer. Hence, a decrease in density leads to an increase in pleomorphism and polymegathism. When endothelial cell density decreases to a critical low threshold (500–1000 cells/mm2), it does not function sufficiently as a barrier to aqueous movement into the stroma. This results in corneal swelling indicated by increased pachymetry readings, which could be significantly asymmetrical in the two eyes. In advanced stages, corneal decompensation can result in bullous keratopathy.9
Detection of FED
The evaluation of cell size, number and morphology is essential to characterise the health of corneal endothelium. Current technologies that provide these data include specular microscopy (see Figure 1: Specular microscopy showing reduced endothelial cell density with pleomorphism and polymegathism and large guttae) and confocal biomicroscopy. Pachymetry will provide corneal thickness measurements which helps in monitoring corneal oedema. These two diagnostic aids are essential at the point of diagnosis as well as further monitoring of the condition.
On the slit lamp, FED can be identified by endothelial guttae seen using specular illumination. Corneal oedema is initially manifest in the posterior stroma adjacent to Descemet’s membrane and just behind Bowman’s membrane, causing a fine grey haze best seen with sclerotic scatter (see Figure 2: Specular illumination showing endothelial guttae and pigment on endothelium. Sclerotic scatter highlights stormal haze. Note different illuminations and features can be seen within the same set up). In addition, swelling of the corneal stroma produces fine vertical striae or wrinkles in Descemet’s membrane. With progression of the disease to the second stage, the entire stroma becomes oedematous, giving the cornea a ground-glass appearance. Epithelial oedema characterises the third stage and fine epithelial microcysts are noted with irregular surface texture observed on sclerotic scatter. As epithelial cysts coalesce they form large intra-epithelial and sub-epithelial bullae. These bullae may rupture, resulting in severe pain and rendering the patient susceptible to infection. In the advanced stage of the disease, there is scarring with the cornea becoming opaque. Corneal sensation and, hence pain, is reduced and with time peripheral corneal vascularisation may occur.8 This end stage is seen less frequently today because of improved success with corneal transplantation.
Differential diagnosis of FED
Central endothelial guttae are an initial manifestation of FED and the dystrophy may or may not be symptomatic. Focal guttae formation without corneal oedema can be observed in interstitial keratitis, macular corneal dystrophy and posterior polymorphous dystrophy. Central herpetic disciform keratitis can mimic FED but the presence of keratic precipitates helps to differentiate the condition. Chandler’s syndrome, one of the triad in iridocorneal endothelial syndrome (ICE) can be confused with FED as its endothelial pattern has a beaten- bronze appearance with overlying corneal oedema. However, iridocorneal adhesions with iris atrophy and unilaterality helps to differentiate the two conditions.10 It is also important to differentiate guttae from pigment dusting which is seen in Krukenberg spindle in pigment dispersion syndrome (PDS), which may also have associated iris transillumination.
Symptoms of FED and cataract
Patients with cataracts and FED often complain of vision loss, which could be due to either condition, or both. In FED, vision is worse in the morning because the tear film becomes hypotonic caused by lack of evaporation associated with eyelid closure, preventing water loss from the corneal epithelium resulting in oedema.Vision improves as the day progresses as evaporation promotes corneal deturgescence. Glare can be particularly bothersome for patients with FED even when cataract is not advanced due to adherent endothelial pigment. The debilitating symptom of glare due to confluent guttae with pigment can occur even when there is little or no stromal oedema and pachymetry is relatively normal (<600μm).2
Managing complications of FED in cataract surgery
Routine cataract surgery has been shown to induce an endothelial cell density loss of 6.3%–12.8% due to ultrasound power during phacoemulsification.11 However, in patients with endothelial disease, cell loss is greater which can result in PBK. If there is awareness of FED, the surgeon’s skill, expertise and surgical technique can minimise endothelial insult, especially in cases where the anterior chamber is shallow. Dense cataracts will require higher energy during surgery; therefore, it may be prudent to avoid waiting until cataracts are mature before they are removed. Modern ophthalmic viscosurgical devices (OVDs) offer further protection from damage to the endothelium. Healon, which is a cohesive viscoelastic composed of sodium hyaluronate, was the first OVD introduced and is used routinely in cataract surgery. Viscoat is a dispersive viscoelastic comprising of sodium hyaluronate and chondroitin sulphate, which offers more protection against cell loss by creating a cushion for the endothelium against mechanical forces of phacoemulsification and is preferable in cases of FED.12 The viscoelastic is later aspirated. Modern machines, which use torsional phacoemulsification compared to longitudinal use less ultrasonography time and dissipate less energy, reducing endothelial insult.13
These days, cataract surgery is planned precisely with highly predictive refractive outcomes to the extent that there are options for clear lens extraction or multifocal intraocular lens implantation for patients who do not wish to wear spectacles. In patients with FED, multifocal IOLs are not suitable due to increased aberration from the cornea. Also, if the patient does require endothelial keratoplasty in future, which usually results in a hyperopic shift of about 0.80D, then refractive outcomes are highly compromised.14
In cases of concomitant FED, post-operative corneal oedema can result in hazy vision which can be worse than prior to cataract surgery and may manifest as early as one or two days post-operatively. The treatment varies according to the severity of the disease. In mild FED, corneal oedema following cataract surgery can be managed by hypertonic sodium chloride 5% drops four to six times a day as well as ointment at night time which works by drawing water out of the cornea thereby reducing oedema.
In cases where intraocular pressure is high, it might be worth reducing this as anterior movement of fluid in the stroma is driven by intraocular pressure. Corneal oedema can be monitored by pachymetry. Surgical intervention is indicated where the cornea is decompensating, creating corneal oedema with bullous keratopathy. In the past, this was managed by penetrating keratoplasty (PK), which replaces the full thickness of the cornea. With advances in keratoplasty there is a move towards disease-specific procedures where the endothelial layers are grafted selectively, namely Descemet stripping endothelial keratoplasty (DSEK) (see Figures 3: DSEK seen in diffuse illumination and 4: DSEK seen in cross-section with direct illumination with narrow slit beam) when created manually, or referred to as Descemet stripping automated endothelial keratoplasty (DSAEK) when the graft is created by a mechanical microkeratome, or more recently Descemet membrane endothelial keratoplasty (DMEK) (see Figures 5: DMEK seen in cross-section with direct illumination and 6: DMEK graft edge interface). The advantages of DSAEK and DMEK over PK is a shorter period of vision restoration (three to six months versus 12 to 18 months) and reduced amount of post-operative astigmatism (average 1.50D versus 6.00- 10.00D) as there is no substantial change to the anterior surface of the cornea and less suture related problems. The difference between DSAEK (see Figure 7: OCT highlighting thickness of DSAEK) and DMEK (see Figure 8: OCT highlighting thickness of DMEK) is that the latter is a more delicate procedure and unlike DSAEK it does not include stromal tissue.
A combined approach?
The decision whether to perform cataract extraction alone or combine with corneal endothelial keratoplasty (EK) in a single procedure is based on a number of factors, including corneal thickness, number and morphology of cells as determined by specular microscopy along with symptoms (variation of vision throughout the day).
To avoid unnecessary cost and delay in visual rehabilitation, Seitzman et al recommended a combined procedure for eyes with preoperative pachymetry measurements of >640μm.15 The combined approach requires a triple procedure of keratoplasty, phacoemulsification and intraocular lens implantation, where the phacoemulsification and intraocular lens implantation is carried out first to prevent endothelial cell damage in the new grafted material.
Combined procedures can have complications of donor graft dislocation. In a recent audit conducted at the Queen Victoria Hospital to compare outcomes ofstaged cataract surgery followed by EK, and combined triple procedure, it was found that complication of graft dislocation was higher at 26.6% (8 out of 30) in the combined procedure compared to 6% (two out of 33) in the staged procedure.16 Although it can be argued that the combined procedure is cost and time saving in terms of visual rehabilitation, patients who had complications and needed further surgical intervention can find it dissatisfying and raise their anxiety levels. If staged, some patients may not even need the EK following cataract surgery if the insult to the endothelium is minimised. Going by Seitzman’s recommendation of doing combined procedure for corneal pachymetry >640μm, it is likely that at this level of thickness FED is fairly advanced and the patient is likely to be symptomatic. Hence, combined procedure would be beneficial in terms of time of visual rehabilitation in these cases.
When assessing cataract patients, it is important to perform a systematic anterior segment assessment with slit lamp and identify comorbidities such as FED, which is often asymptomatic in the initial stages. Early detection will help to plan appropriate surgical management as well as provide information to the patient regarding risks and help prepare them for a potentially unfavourable outcome. With a compromised corneal endothelium, it is important to use a surgical technique that is the least traumatic as well as provide maximum protection to the corneal endothelium with use of dispersive OVD. As dense cataracts require higher phaco energy, it may be prudent for the optometrist to refer the patient when the cataract is not too dense, even if this contravenes local guidelines in cases of concomitant FED to minimise complications and improve visual rehabilitation.
In patients with cataract and early FED, cataract extraction alone may be preferable
especially if pachymetry shows corneal thickness to be <640μm. However, if corneal oedema follows, it can be treated with hypertonic saline 5% drops to reduce the corneal swelling. In cases where the cornea is decompensating, then EK will be indicated. Decisions to opt for combined procedures may be governed by symptomatic FED as well as the pachymetry readings.
About the authors
Shruti Malde MCOptom, Dip Tp (AS), Dip Tp (SP), has worked in hospital optometry for 20 years and has been in her current post at Queen Victoria Hospital, East Grinstead, for four years. Her extended role as a specialist optometrist includes reviewing new and post-op cataract, glaucoma cases and assisting in corneal clinics including undertaking collagen cross-linking follow-up checks. She has a diploma in Therapeutics Additional Supply and Supplementary Prescribing. Damian Lake MD, MBChB, FROphth, is the corneal lead consultant, clinical director for ophthalmology and medical advisor to the Eye Bank at Queen Victoria Hospital, East Grinstead. He specialises in corneal transplants, ocular surface stem cell and amniotic membrane transplants, keratoprosthesis, artificial iris, secondary intraocular lenses, complex cataract surgery, laser vision correction, keratoconus rehabilitation, and inflammatory ocular surface conditions.
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- Maar N, Graebe A, Schild G, et al. Influence of viscoelastic substances used in cataract surgery on corneal metabolism and endothelial morphology: comparison of Healon and Viscoat. J Cataract Refract Surg. 2001; 85:18-20
- Doors M, Berendschot TT, Touwslager W et al. Phacopower modulation and the risk for postoperative corneal decompensation: a randomized clinical trial. JAMA Ophthalmology. 2013 Nov; 131(11):1443-50
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- 1Sykakis E, Lam FC, Georgoudis P et al. Patients with Fuchs Endothelial Dystrophy and Cataract Undergoing Descemet Stripping Automated Endothelial Keratoplasty and Phacoemulsification with Intraocular Lens Implant: Staged versus Combined Procedure Outcomes. Journal of Ophthalmology. Volume 2015 (2015), Article ID 172075