Ординатура / Офтальмология / Английские материалы / Ocular Periphery and Disorders_Dartt, Bex, Amore_2011

Figure 2 Patient with two intracorneal ring segments (Intacs).

These presbyopic inlays are designed to be implanted in the nondominant eye and have a pinhole optic, which increases the depth of focus. They are currently under investigation in the United States and Europe.

Intracorneal Rings (ICR)

Since 1999 the use of ICR segments, also known as Intacs, has been approved by the United States FDA for the correction of low myopia (less than 4 D) and low astigmatism ( 1 D). These ring segments are curved and made of polymethylmethacrylate. They can be inserted into the peripheral cornea through corneal channels, which are created by a microkeratome or by a femtosecond laser, at about 70% of the corneal depth (Figure 2). They aim to expand and flatten the corneal surface.

ICR have some important advantages over laser refractive surgery: there is no abrasion of the cornea, less risk of corneal haze or scarring, the visual axis is spared from treatment, there is no flap creation and, therefore, no flaprelated complications, and the procedure is reversible.

Complications following ICR implantation include induced astigmatism – which is the most common complication – extrusion of the ring, dry eye syndrome, and infectious keratitis.

In the treatment of low myopia, the visual results of ICRs seem to be similar to the results following laser refractive surgery. However, ICRs are mainly used to improve visual outcomes in patients with keratoconus, post-LASIK ectasia, or other ectatic disorders.

Conclusion

In conclusion, for the treatment of patients with low-to- moderate myopia, PRK, LASIK, and LASEK have all shown to produce stable and predictable results with an excellent safety profile. Patient selection is crucial to ensure high postoperative patient satisfaction and to

diminish the risks of adverse effects. LASIK has the advantage of rapid visual recovery and minimal discomfort and, therefore, has become the most widely performed refractive surgery technique, associated with high patient satisfaction. However, mechanical microkeratome-assisted LASIK displays more complications due to the creation of a flap and might cause more induced HOAs, which is why some surgeons have switched to PRK or LASEK. In the near future, FS-LASIK might become the recommended treatment, but a longer follow-up is needed to ensure longterm stability and safety.

See also: Cornea Overview; Hyperopia; Myopia; Refractive Surgery; The Surgical Treatment for Corneal Epithelial Stem Cell Deficiency, Corneal Epithelial Defect, and Peripheral Corneal Ulcer.

Further Reading

Alio, J. L., Muftuoglu, O., Ortiz, D., et al. (2008). Ten-year follow-up of laser in situ keratomileusis for myopia of up to –10 diopters.

American Journal of Ophthalmology 145: 46–54.

Choi, D. M., Thompson, R. W., and Price, F. W. (2002). Incisional refractive surgery. Current Opinion in Ophthalmology 13: 237–241.

Fan-Paul, N. I., Li, J., Miller, J. S., and Florakis, G. J. (2002). Night vision disturbances after corneal refractive surgery. Survey of Ophthalmology 47: 533–546.

Guell, J. L. (2005). Are intracorneal rings still useful in refractive surgery?

Current Opinion in Ophthalmology 16: 260–265. Katsanevaki, V. J., Kalyvianaki, M. I., Kavroulaki, D. S., and

Pallikaris, I. G. (2007). One-year clinical results after epi-lasik for myopia. Ophthalmology 114: 1111–1117.

Nuijts, R. M., Nabar, V. A., Hament, W. J., and Eggink, F. A. (2002). Wavefront-guided versus standard laser in situ keratomileusis to correct low to moderate myopia. Journal of Cataract and Refractive Surgery 28: 1907–1913.

Pop, M. and Payette, Y. (2004). Risk factors for night vision complaints after LASIK for myopia. Ophthalmology 111: 3–10.

Rajan, M. S., Jaycock, P., O’Brart, D., Nystrom, H. H., and Marshall, J. (2004). A long-term study of photorefractive keratectomy; 12-year follow-up. Ophthalmology 111: 1813–1824.

Sakimoto, T., Rosenblatt, M. I., and Azar, D. T. (2006). Laser eye surgery for refractive errors. Lancet 367: 1432–1447.

Slade, S. G. (2008). Thin-flap laser-assisted in situ keratomileusis.

Current Opinion in Ophthalmology 19: 325–329.

Sugar, A., Rapuano, C. J., Culbertson, W. W., et al. (2002). Laser in situ keratomileusis for myopia and astigmatism: Safety and efficacy: A report by the American Academy of Ophthalmology.

Ophthalmology 109: 175–187.

Sweeney, D. F., Vannas, A., Hughes, T. C., et al. (2008). Synthetic corneal inlays. Clinical and Experimental Optometry 91: 56–66.

Tahzib, N. G., Bootsma, S. J., Eggink, F. A., Nabar, V. A., and Nuijts, R. M. (2005). Functional outcomes and patient satisfaction

after laser in situ keratomileusis for correction of myopia. Journal of Cataract and Refractive Surgery 31: 1943–1951.

Taneri, S., Zieske, J. D., and Azar, D. T. (2004). Evolution, techniques, clinical outcomes, and pathophysiology of LASEK: Review of the literature. Survey of Ophthalmology 49: 576–602.

Waring, G. O., Lynn, M. J., and McDonnell, P. J. (1994). Results of the prospective evaluation of radial keratotomy (PERK) study 10 years after surgery. Archives of Ophthalmology 112: 1298–1308.

Relevant Website

http://www.intacsforkeratoconus.com – Intacs Corneal Implants.

Glossary

Contact lens-induced papillary conjunctivitis (CLPC) – Enlarged papillae accompanied by redness of the upper palpebral conjunctiva. Symptoms include discomfort, itching, mucous discharge, and foreign body sensation. Corneal infiltrates – Corneal inflammatory

response which appears as single or multiple, focal or diffuse lesions in the corneal stroma.

Endothelial polymegethism – Variation in the size of the endothelial cells of the cornea as a result of disturbed metabolism.

HEMA – Hydroxyethylmethacrylate monomer forming the basis of many soft contact lens material polymers. Hypermetropia – Also known as farsightedness, it is a defect of vision caused by an imperfection in the eye (often when the eyeball is too short or when the lens cannot become round enough), causing difficulty focusing on near objects.

Lens-induced chronic hypoxia – Corneal oxygen deprivation that results from contact lenses that greatly impede oxygen diffusion to the cornea. Chronic hypoxia may cause changes in corneal structure and neovascularization.

Multipurpose solutions (MPSs) – Solution for cleaning, rinsing, disinfecting, and storing your contact lenses.

Myopia – The ability to see close objects more clearly than distant objects. Myopia can be caused by a longer-than-normal eyeball or by any condition that prevents light rays from focusing on the retina. Orthokeratology – The practice of reshaping the cornea by wearing specially designed rigid contact lenses. These lenses are usually worn only during sleep and they reshape the front surface of the eye, correcting the refractive error and allowing clear vision. PMMA – Polymethylmethacrylate material used for oxygen impermeable hard contact lenses.

RGP – Rigid gas permeable materials used for oxygen permeable hard contact lenses.

Superior epithelial arcuate lesions (SEALs) –

Whitish, opalescent lesions, located adjacent or at the superior limbus, caused predominantly by a mechanical interaction between the (usually) silicone hydrogel or hydrogel contact lens, the eyelid, and the superior peripheral cornea.

Introduction

Contact lenses provide a safe and reversible means of refractive error correction; lenses are currently worn by 150 million individuals worldwide. Contact lenses have many optical, sporting, cosmetic, therapeutic, and vocational advantages over conventional spectacles. The vast majority of wearers use contact lenses for the correction of simple low refractive errors but other applications include presbyopia, astigmatism, high refractive error, and other medical, cosmetic, or therapeutic indications.

Given their close association with the ocular surface, contact lens wear may have an impact on ocular surface anatomy and physiology and they may be associated with adverse effects, including ocular surface infection or inflammation. The impact of contact lens wear varies with lens type, mode of wear, indication for lens wear, and with wearer factors including demographics, hygiene, compliance, and behavior factors.

Types of Contact Lenses

Hard lenses, made from polymethylmethacrylate (PMMA), were first available in 1934 and soft lenses during the 1960s. Lens materials have evolved since with the advent of gas permeable rigid materials and more recently silicone hydrogel materials. An ideal material and lens design would maintain normal ocular surface physiology, have a low rate of complications, provide vision correction, and be comfortable during wear (Table 1 and Figures 1–6).

Probably the most exciting recent innovation in the field has been the introduction of silicone hydrogel materials. The high oxygen permeability of these new siliconebased products has limited the effects of hypoxia and largely eliminated a range of physiological complications such as corneal edema, microcysts, corneal vascularization, endothelial polymegethism, overwear syndrome, and corneal exhaustion.

Lenses may be worn on a daily wear basis, where they are removed, cleaned and disinfected overnight, and reinserted the following day. Daily lens use is the most common modality prescribed. Complication rates are generally lowest with this wear modality; however, conditions associated with toxic or allergic responses to lens care products occur more commonly with daily lens use. Daily disposable contact lenses (lenses worn once during the day and discarded on removal) have eliminated many

Orthokeratology lenses: generally highly oxygen permeable rigid gas permeable materials

. Flexible polymers which conform to the shape of Figure 3 the cornea and limbus

. Average lens diameter 13–15 mm

. Water content of polymer determines oxygen permeability

Silicone hydrogel: silicone incorporated

Figure 3 Hydrogel lens of 14 mm diameter.

Figure 4 Hybrid lens on eye.

Figure 5 Rigid lenses from left to right: corneal RGP; orthokeratology RGP, mini-scleral, full scleral.

Figure 6 Full scleral contact lens on eye.

complications related to care solution use and those due to inadequate contact lens or storage case hygiene. A proportion of daily lens users (13–23%) report occasional unscheduled overnight use of lenses of up to one night per week. Certain lenses may be prescribed for overnight use, where they are worn continuously for up to 30 consecutive nights.

How Contact Lens Wear Affects

the Ocular Surface

Hydrogel and silicone hydrogel contact lenses are on average 2–3 mm larger than the cornea and overlay the limbus and surrounding bulbar conjunctiva, consequently contact lenses interact directly with the corneal, limbal, bulbar, and tarsal conjunctival epithelia, and with the tear film. Their impact on the ocular surface can be characterized as follows.

Effects of Contact Lens Wear on the Corneal and Limbal Epithelium

Lens-induced chronic hypoxia can lead to changes in the corneal epithelium such as thinning, lower oxygen uptake rates, and increased microcysts. In addition, limbal hyperemia is increased and encroachment of blood vessels into the corneal stroma can occur. The smaller diameter of rigid lenses results in less interaction between the lens and limbal or conjunctival epithelium, generally less corneal hypoxia and greater tear exchange compared with soft contact lenses.

Epithelial microcysts are one of the more obvious clinical markers of hypoxia, appearing as small, irregular dots in retro illumination of the cornea with a slit lamp biomicroscope at high magnification. They are comprised of degenerated cellular material and are most often seen after 3 months of extended wear of low oxygen transmissible

lenses. They are transitory, exhibiting a spike in numbers approximately 1 month after hypoxic stress is removed and returning to normal within 3 months.

All contact lenses slow the corneal epithelial cell renewal cycle by slowing epithelial cell proliferation and migration and lowering the exfoliation rate. At the limbus, stem cells continually provide new basal corneal epithelial cells, where the rate of production increases during ocular surface damage. Recurrent erosion, chronic inflammation, and blood vessel growth onto the cornea (vascularization) can occur as a result of compromise to the limbal stem cells. Basal epithelial cells produced from slow cycling stem cells replicate and migrate horizontally, differentiating upward, before undergoing either apoptosis (programmed cell death) or necrosis and exfoliation into the precorneal tear film. Soft contact lens wear, in particular, lens-related hypoxia, has been reported as a possible cause of limbal stem cell damage. To a lesser extent contact lenses may have a mechanical effect on the limbal stem cells, which are protected somewhat due to their location at the level of the basal epithelium.

Alteration of the Lens: Cornea Resurfacing

Mechanism

The precorneal tear film maintains the normal optical, lubrication, and defence functions of the ocular surface. Wear of a contact lens may destabilize the tear film by compartmentalizing the tear film into prelens and postlens regions, by changing the tear film structure and components and by reducing tear exchange.

Compared with the normal precorneal tear film, the prelens tear film is thinner, less stable, and exhibits higher evaporation. The increased evaporation rate is thought to be related to a thinner lipid layer which is more prone to contamination. A thinner lipid layer, lens dehydration, and an unstable tear film can lead to corneal epithelial dessication.

All contact lenses inhibit normal tear exchange by trapping debris, toxins, antigens, and microorganisms beneath the lens and interfering with the normal resurfacing action of blinking. Increasing the retention time of metabolic debris, toxins, or antigens at the ocular surface has been implicated in the development of inflammatory conditions. The rate of tear exchange varies with lens type, material and wearer characteristics. For example, rigid gas permeable (RGP) contact lenses allow more rapid tear exchange than hydrogel or silicone hydrogel lenses and are associated with a lower rate of inflammatory complications compared to soft lens wear.

Adverse Events

Inflammation

Corneal inflammation occurs relatively often in contact lens wear, affecting 7% of wearers. The risk of inflammation

varies with different lens materials and wear modalities. The severity of inflammation varies and several systems have been used to characterize and classify corneal inflammation. Contact lens-related corneal inflammation is characterized by white blood cells, usually polymorphonuclear leukocytes, invading the cornea stroma (infiltrates). The infiltrates appear as small, usually round, opaque lesions (focal) or dispersed in a haze (diffuse). Usually limbal and bulbar redness accompanies the infiltrates. Epithelial damage can be present. Inflammation can be as a result of mechanical trauma but more often results from toxic reactions to bacteria. In the closed eye environment, bacterial toxin concentration behind the lens as well as compromise to the normal lid-tear resurfacing and alteration of tear defence proteins may lead to more frequent inflammation in extended compared to daily wear.

Contact lens-induced papillary conjunctivitis (CLPC) is an inflammatory reaction of the upper palpebral conjunctiva, caused by mechanical trauma and/or allergic response to the lens or deposits on the surface of the lens. It is the most common contact lens-related adverse event that leads to discontinuation of lens wear. Clinically, it presents as raised papillae, which comprise lymphocytes and plasma surrounding central blood vessels and associated hyperemia. There are two forms of CLPC, one that involves the entire upper palpebral area (generalized) and the other a small cluster (localized). CLPC is more frequent in soft than rigid lenses, and more common in extended compared to daily wear. The generalized form is more common in softer, hydrogel lenses which attract more protein deposits; this form likely represents a hypersensitivity (both type I and type IV) response, whereas localized disease is more likely to be found with the stiffer silicone hydrogel lenses and is thought to be related to mechanical trauma.

Infection

Corneal infection is a rare but severe complication of contact lens wear, affecting 4 per 10, 000 wearers per year, with higher rates (20 per 10, 000) per year in overnight lens use. These estimates have remained remarkably consistent over a 20-year period, despite advances in contact lens materials, wear modalities, and care system technologies. Permanent vision loss occurs in 6 per 100, 000 wearers per year or in 10–15% of cases of infection. Lower rates of severe keratitis and vision loss have been reported with daily disposable contact lens use. A poorer disease outcome is strongly associated with recovery of an environmental pathogen and a delay in receiving appropriate treatment.

Unlike corneal infections in noncontact lens wearers, Pseudomonas aeruginosa is the most common pathogen associated with contact lens-related disease, accounting for 50–60% of culture proven cases. More recently, environmental organisms such as Acanthamoeba and the fungi

Fusarium have been associated with outbreaks of disease, particularly disease linked with the use of specific multipurpose solutions (MPSs). In the case of Acanthamoeba keratitis, strong links with contaminated water have been identified.

Mechanical effects

Contact lenses can cause mechanical effects on the cornea due to their physical presence. For soft contact lenses, superior epithelial arcuate corneal lesions (SEALs), white heaped lesions occurring adjacent to and concentric with the superior limbus are thought to be due to a combination of tight upper-lid pressure, stiffness of the lens material, poor surface, and tight fitting of soft lenses. These are usually associated with foreign body and discomfort symptoms and resolve with interruption to lens wear within 1 week. Erosions, a full thickness epithelial loss, appear as a plug of epithelium that has been lifted off the cornea. Resolution is rapid and often results in clumping of the epithelial cells as healing takes place. Care must be taken to observe good hygiene and not patch the lesion, as the break in the epithelium renders the cornea more prone to infection. Sometimes prophylactic antibiotic therapy is used. Symptoms can be quite painful and can be eased by use of ocular lubricants. For RGP lenses, the most common mechanical effect is abrasion due to debris trapped behind the contact lens. Corneal abrasions are more commonly seen with rigid lenses compared with soft. Often the patient is symptomatic despite quite spectacular appearances; resolution is rapid, usually within a day or two. Abrasions can also occur due to fingernail injuries on removal of lenses.

Current Hot Topics in Contact Lens

Research

Contact Lens Care Products

MPSs dominate the CL care market and are used by 99% of soft lens wearers. In recent years, the industry has been focused on comfort and convenience for the wearer, formulating new preservatives and incorporating comfort additives into care products.

Corneal staining (visualization of damaged epithelial cells by instillation of sodium fluorescein) is the most reliable clinical way to assess corneal integrity. Solutionrelated corneal staining has been reported from a 2-h provocative test and over 3 months of lens wear with a range of lens and solution combinations. Performance has not been predictable in terms of solution preservative or across different silicone hydrogel lens types, likely due to the more complicated lens chemistry compared to hydrogel lenses. Solution-related corneal staining has been associated with decreased comfort and increased

risk of low-grade inflammatory events. MPSs have been associated with decreased epithelial barrier function and increased susceptibility to bacterial binding; however, no evidence to date shows that solution-related staining is a risk factor for infection. Further exploration of the mechanisms and implications of shortand long-term corneal staining is underway.

Corneal Infection

Other than overnight wear of contact lenses, a range of hygiene, compliance, and demographic factors have been consistently associated with disease. In contemporary lens wearers these include increasing the degree of lens use in daily wear, poor-storage case hygiene, smoking, Internet purchase, less than 6 months wear experience, and socioeconomic class. Further study is directed toward exploration of new risk factors, particularly establishing the impact of wearer risk behavior such as internet purchase: evaluation of specific hygiene practice such as rub and rinse and establishing the impact of second generation silicone hydrogel lens materials on the risk of infection. Ongoing surveillance enables monitoring of disease outbreaks and new or unusual causative organisms.

In corneal infection associated particularly with daily wear of contact lenses, the storage case has been identified as the source of organisms. This has resulted in the uptake of antimicrobial technologies, such as silver, into contact lens storage cases to limit microbial adhesion and colonization of the contact lens storage case. Early reports indicate some reduction in levels of certain microorganisms, but the long-term impact of these technologies in clinical use has not yet been established.

Orthokeratology

Orthokeratology is a nonsurgical approach to temporarily correct or eliminate refractive error through rigid lens wear to reversibly change the curvature of the cornea. More recent approaches include using specially designed rigid contact lenses worn overnight to enable clear vision without lens wear during the daytime. In the case of myopia correction, a reverse-geometry lens with a base curve flatter than the peripheral curve of the back surface is worn. The reduction in myopia occurs through central corneal epithelial thinning. While these effects are reversible there is discussion whether the impact of orthokeratology lenses on the corneal epithelium increases the risk of corneal infection. Ongoing studies endeavor to optimize the refractive effects both in myopia and hypermetropia, to understand the mechanisms in epithelial thinning and to establish whether orthokeratology can be used to permanently reduce or eliminate refractive error or to prevent myopia progression.

Summary

A range of materials and wear modalities are available in contemporary contact lens practice to correct a wide range of refractive errors, potentially to slow or prevent refractive error development and to meet other medical or cosmetic requirements. Contact lenses interact closely with the ocular surface and all lenses, to a lesser or greater degree, will impact on the conjunctiva, lid, cornea, and tear film physiology. While the majority of their effects and complications are reversible and nonsevere, corneal infection remains the most severe response which can potentially result in vision loss due to scarring and perforation. Safe contact lens wear requires awareness by wearers to ensure that their eyes ‘‘Feel good, see well and look good’’ at all times. In the rare event of corneal infection, morbidity can be limited by prompt treatment by the practitioner. Recent outbreaks of corneal infection caused by unusual environmental organisms have resulted in the industry demanding more appropriate care solution testing for licensing purposes, and improved guidelines and recommendations for contact lens wearers. Research into the impact of care solutions on the ocular surface, optimization of orthokeratology, eludication of new risk factors for corneal infection, and ongoing disease surveillance will better inform practitioners and wearers and result in improved outcomes for contact lens wearers.

See also: Corneal Epithelium: Transport and Permeability; Corneal Epithelium: Response to Infection; Immunopathogenesis of Pseudomonas Keratitis; Inflammation of the Conjunctiva.

Further Reading

Carnt, N., Jalbert, I., Stretton, S., Naduvilath, T., and Papas, E. (2007). Solution toxicity in soft contact lens daily wear is associated with corneal inflammation. Optometry and Vision Science 84: 309–315.

Dart, J. K. G., Radford, C. F., Minassian, D., Verma, S., and Stapleton, F. (2008). Risk factors for microbial keratitis with contemporary contact lenses: A case-control study. Ophthalmology 115: 1647–1654. e1643.

Fon, D., Reyers, M., Terry, R., and Williams, L. (2000). The IACLE Contact Lens Course, 1st edn., vols. 2 and 8. Sydney: The International Association of Contact Lens Educators.

Holden, B. A., Sweeney, D. F., Vannas, A., Nilsson, K. T., and Efron, N. (1985). Effects of long-term extended contact lens wear on the human cornea. Investigative Ophthalmology and Visual Science 26: 1489–1501.

Keay, L., Edwards, K., Naduvilath, T., Forde, K., and Stapleton, F. (2006). Factors affecting the morbidity of contact lens related microbial keratitis: A population study. Investigative Ophthalmology and Visual Science 47: 4302–4308.

Keay, L., Jalbert, I., Sweeney, D. F., and Holden, B. A. (2001). Microcysts: Clinical significance and differential diagnosis.

Optometry (St Louis, MO) 72: 452–460.

Li, S. L., Ladage, P. M., Yamamoto, T., et al. (2003). Effects of contact lens care solutions on surface exfoliation and

bacterial binding to corneal epithelial cells. Eye Contact Lens 29: 27–30.

O’Hare, N., Stapleton, F., Naduvilath, T., et al. (2003). Interaction between the contact lens and the ocular surface in the aetiology of superior epithelial arcuate lesions. Advances in Experimental Medicine and Biology 506: 973–980.

Ren, D. H., Petroll, W. M., Jester, J. V., and Cavanagh, H. D. (1999). The effect of rigid gas permeable contact lens wear on proliferation of rabbit corneal and conjunctival epithelial cells. CLAO Journal 25: 136–141.

Stapleton, F., Keay, L., Jalbert, I., and Cole, N. (2007). The epidemiology of contact lens related infiltrates. Optometry and Vision Science 84: 257–272.

Stapleton, F., Keay, L., Edwards, K., et al. (2008). The incidence of contact lens related microbial keratitis. Ophthalmology 115: 1655–1662.

Swarbrick, H. A. (2006). Orthokeratology review and update. Clinical and Experimental Optometry 89: 124–143.

Sweeney, D. F., Jalbert, I., Covey, M., et al. (2003). Clinical characterisation of corneal infiltrative events observed with soft contact lens wear. Cornea 22: 435–442.

Thai, L. C., Tomlinson, A., and Doane, M. G. (2004). Effect of contact lens materials on tear physiology. Optometry and Vision Science 81: 194–204.

Truong, T., Wofford, L., and Lin, M. (2005). Effects of lens-care solutions on corneal epithelial barrier function. Optometry and Vision Science 82: E-Abstract 055009.

Vermeltfoort, P. B. J., Hooymans, J. M. M., Busscher, H. J., and van der Mei, H. C. (2008). Bacterial transmission from lens storage cases to contact lenses – effects of lens care solutions and silver impregnation of cases. Journal of Biomedical Materials Research 87B(1):

237–243.

Glossary

Chemosis – Swelling of the iris due to swelling of the bulbar conjunctiva.

Corneal verticillata – Congenital whorl-like opacities in the cornea.

DSAEK – Descemet’s Stripping Automated Endothelial Keratoplasty, a form of keratoplasty which involves the removal of the host’s central Descemet’s membrane and corneal endothelium, which is subsequently replaced with a disc shaped graft of donor corneal stroma, Descemet’s membrane and endothelium.

Follicles – Lymphoid tissue in the conjunctival stroma.

Fuchs’ dystrophy – A common adult-onset form of corneal dystrophy with autosomal dominant inheritance. In this disease, the endothelial cells in the cornea gradually deteriorate.

Guttae – Drop-like.

Keratic precipitates – Fibrous deposits on the posterior surface of the cornea, usually associated with uveitis.

Laser-assisted in situ keratomileusis (LASIK) –

Refractive surgery to correct myopia, hyperopia, and astigmatism.

Lattice dystrophy – Hereditary corneal dystrophy in which there is an accumulation of amyloid deposits throughout the middle and anterior stroma of the cornea.

Lenticle – Relating to the lens.

Pappillas – Small projection of tissue commonly triggered by constant irritation of the conjunctiva by contact lenses.

Pachymetry – Measurement of the thickness of the cornea.

Pigment dispersion syndrome (PDS) – Condition when the iris pigment epithelium and the lens come into contact. This leads to mechanical disruption of the iris resulting in release of pigment granules into the posterior chamber, which follows the flow of aqueous into the anterior chamber angle. The pigment can block the aqueous outflow resulting in elevated intraocular pressure with possible damage to the optic nerve.

Posterior polymorphous dystrophy – Disease involving metaplasia and overgrowth of corneal endothelial cells.

Pseudoexfoliation syndrome – Characterized by flakes of granular material at the pupillary margin of the iris and throughout the inner surface of the anterior chamber. It is also associated with secondary open-angle glaucoma.

Pseudophakic bullous keratopathy – Corneal edema occurring following cataract extraction. Sclerotic scatter – Biomicroscope illumination that scatters light throughout the cornea.

Subluxation – Partial dislocation of an organ.

Slit-Lamp Biomicroscopy

The slit-lamp biomicroscope is a versatile device that is the primary diagnostic instrument used during the clinical examination of the cornea and the external structures of the eye and adenexa. It has two primary components mounted on a common axis – the slit illuminator and the biomicroscope. The slit-beam-illumination unit is essentially a projector with a light beam that is adjustable in height, width, direction, and intensity. The examiner can create a sharply focused narrow slit beam which can illuminate and isolate fine detail in otherwise translucent tissue. The biomicroscope component is a binocular Galilean telescope that can produce excellent resolution at multiple magnifications. A headrest stabilizes the patient, and adjustable oculars allow the examiner to focus a stereoscopic image.

The biomicroscope and the illuminator are arranged to be parfocal (focus on the same plane) and isocentric (the slit beam is centered in the field of view), which is necessary for its function. This essential setup allows for both direct illumination and – with shifting of the alignment – indirect illumination.

During diffuse illumination, the light beam is broadened to its largest aperture and kept at both low magnification and reduced intensity. The illuminator is directed at the eye from an oblique angle and rotated through its arc of travel from side to side. When the light is applied tangentially, surface changes are enhanced and dimensionalized through the effect of creating highlights and shadows. Subtle alterations from normal topography become more clearly noticeable. Direct illumination can highlight conjunctival changes such as chemosis, follicles, and papillae and can further direct the examiner’s exam.

Broad-beam illumination can help the examiner visualize opaque lesions that may reflect or absorb light. This technique can be invaluable in evaluating the anterior segment structures from the cornea to the iris. When no abnormalities are seen with this technique, other forms of illumination should be explored.

Narrow-beam illumination allows the examiner to evaluate transparent tissues such as the cornea and lens through virtual cross-sections. When used under high magnification, the principal layers of the corneal can be distinguished clearly with great precision. In addition, a narrow beam can be used to identify the presence of anterior chamber cell and flare. Cell and flare is best seen against the background of the dark pupil with an intense but shortened slit light beam.

Specular reflections represent the normal light reflexes that bounce off of an ocular surface. These reflections actually correspond to the mirrored reflections from the light source itself. The most important application of specular reflection is in the evaluation of the corneal endothelium. This involves arming the slit beam at an angle of 40–60 from the viewing arm and using a short slit. Then, the specular reflection of the light bulb’s filament is identified on the tear film. Adjacent to this area (on the side away from the light source), the less bright endothelial reflection can be viewed. Moving the biomicroscope slightly forward will bring the endothelial cellular detail into focus. A magnification of 25 to 40 is usually needed to obtain a clear view of the endothelial mosaic. Cell density and morphology can be evaluated; guttae and keratitis precipitates will appear as nonreflective dark areas.

Indirect illumination can provide unique information. In this method of illumination, the light beam is directed to an area adjacent to the area needing to be examined. Under higher magnification powers, the light beam may need to be decentered from the normal isocentric position. The area being evaluated is seen via retro-illumination from the deeper layers. This method is highly effective for observing detail in areas that are deep to more anterior lesions which may prevent light from penetrating through. For example, an embedded foreign body that is obscured by tissue reaction can be better mapped out through proximal illumination.

Sclerotic scatter takes advantage of the optical phenomenon total internal reflection seen in the cornea. The examiner should direct a de-centered – but intense – light beam at the corneoscleral junction. In a normal cornea the light is only seen where it intersects and reflects the sclera. A ring of light around the limbus is seen, but the cornea will remain dark against an essentially dark background. In an abnormal cornea, the light that is reflected at the sclera will illuminate an abnormality. Thus, abnormalities can be seen in totality and be better recognized as part of a broader disease pattern (e.g., corneal verticillata).

Retro-illumination of the iris combines both direct illumination and indirect retro-illumination to reveal

different details about the area being examined. When the light beam is directed tangentially toward the cornea, direct retro-illumination from the iris can reveal opaque corneal lesions. In contrast, the areas adjacent to the light beam can reveal subtle refractile changes of lower density in the cornea, through indirect retro-illumination from the iris. The interface against both light and dark backgrounds is what shapes the light to reveal details through retro-illumination. Examples of corneal pathology which are best revealed through retro-illumination from the iris include folds in Descemet’s membrane, and the linear stromal corneal changes in Lattice dystrophy. Retroillumination from the fundus reflects light from the retinal pigment epithelium through the pupil to reveal changes in the cornea, lens, and anterior vitreous. A well-dilated pupil will achieve the most effect because light will not be scattered from the iris. In contrast to sclerotic scatter where abnormalities are best seen against a dark background, this technique uses brightfield illumination to reveal pathology. Lenticular changes, such as posterior subcapsular cataracts or subluxation, can be clearly visualized against the color reflected from the retinal pigmented epithelium. Retroillumination of the iris and lens can reveal iris defects seen in glaucomatous diseases such as pigment-dispersion syndrome and pseudoexfoliaiton syndrome.

Specular Microscopy

Specular microscopy was developed by David Maurice in 1968. This device was used to examine the corneal endothelium, ex vivo, in the laboratory. This first microscope had an effective magnification of 500 , but was not practical for clinical use. In 1975, Bourne, Kaufman, and Lange developed clinical specular microscopes. Specular reflections arise from light which is reflected from the interfaces of materials with different indices of refraction. This occurs when the angle of incidence is equal to the angle of reflection. Thus, the difference between the index of refraction between the corneal endothelium and the aqueous produces a specular reflection. Many types of specular microscopes exist, which can be divided into contact and non-contact, and clinical (horizontal) and upright (which is used by eyebanks). Other types of specular microscopes are capable of visualizing other layers within the cornea.

The advent of the specular microscope allowed the ophthalmologist direct observation of the corneal endothelium in patients with Fuchs’ dystrophy, posterior polymorphous dystrophy, psuedophakic bullous keratopathy, and other disorders of the corneal endothelium (Figure 1). If the cornea is significantly edematous, the specular reflection can be masked – which prohibits the visualization of the corneal endothelium. Specular microscopy is also used by eye banks to examine the corneal endothelium of

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Figure 1 The specular photomicrograph shows a typical image from a noncontact specular microscope. From the information in this image, a cell count can be obtained and the degree of polymegathism and pleomorphism can be assessed.

donor corneas. The endothelial cell counts – which are reported as cells per square millimeter – are used to determine the suitability and health of the transplant tissue. Corneal endothelial cells typically demonstrate a hexagonal shape. A deviation from the normal hexagonal endothelial mosiac is termed pleomorphism. Although the size of corneal endothelial cells may vary slightly, in a healthy cornea, the cells should be similar in size. When there is great variablity in cell size, this is termed polymegathism.

Confocal Microscopy

Confocal microscopy employs a point source of light, which is focused on a thin section of the specimen. The confocal point detector is used to collect the resulting reflected signal. The use of a pinhole light source and its conjugate pinhole detector trades field of view for enhanced resolution by eliminating light which is reflected from structures above and below the focal plan under observation. A full field of view must be obtained by scanning many regions of the specimen. This can be achieved by rotating discs that contain multiple conjugate point detec- tors-pinhole light sources that allow for even scanning of the tissue. Other confocal systems use a slit beam which scans the specimen with a mechano-optical mirror system. White-light or a laser can be used at the light source. These systems are respectively termed white light confocal microscopes or laser scanning confocal microscopes.

The confocal microscope examines the cornea in coronally oriented sections versus the typical sagittal sections that are common to most histological tissue preparations (Figure 2). The corneal epithelium appears as a large cellular mosaic with bright, hyper-reflective central nuclei (Figure 2(a)). The basal epithelium consists of

smaller cells and, generally, does not exhibit visible nuclei (Figure 2(b)). The corneal stroma appears as a collection of hyper-reflective, bean-shaped keratocyte nucei (Figure 2(d) and 2(e)). The dendritic-appearing cell bodies of the keratocytes are only visible when the keratocytes are active. Corneal nerves can be seen passing through the stroma (Figure 2(c)). The deeper corneal nerves are large compared to the subepithelial nerve plexus, which resembles a fine filamentous membrane (Figure 2(e)). The corneal endothelium appears next (Figure 2(f)). Because the confocal microscope is able to eliminate aberrant light, corneal edema rarely obscures the corneal endothelium – unlike in the specular microscope.

Images that are obtained during confocal microscopy are native video; individual still-frames can be captured, as well as video. The images can be stored digitally or on video tape. Because of the ability to scan through the cornea and other tissues, video images can be particularly informative. Furthermore, the images are typically registered by z-axis location (depth within the cornea or other tissue). Thus, three-dimensional (3D) reconstructions can be produced which reveal ex vivo histopathology – like those depicting sections of the cornea.

The advantages of confocal microscopy are as follows:

(1) the resolution can be better than the resolution obtained with the conventional light microscopy, allowing for imaging of the epithelial surface, stroma, nerves, and endothelium (2) high-resolution images can be obtained in vivo without the need for staining or processing of the cornea.

The clinical applications of confocal microscopy include the identification of corneal infectious agents, including bacteria, fungi, and Acanthamoeba. It has been used in clinical research to assess the effect of corneal wound-healing responses after refractive surgery and to characterize corneal dystrophies (Figure 3). Because the device can measure in the z-axis, it can be used to determine the depth of structures within the cornea, such as the thickness of the laser-assisted in situ keratomileusis (LASIK) flap or the residual bed, and the depth of corneal scars. These devices may also be useful in diagnosing neoplasia of the cornea and conjunctiva.

Ultrasound Biomicroscopy

High-frequency ultrasound biomicroscopy (UBM) produces high-resolution images of the anterior segment. Cross-sectional images of the eye are produced using a frequency range of 25–100 MHz. Resolution ranges from 20 to 100 mm. Higher frequencies provide higher resolution but the signal is increasingly attenuated, thereby limiting penetration of the signal. Newer technology can amplify the returning signal based on the depth of the structure under examination. The transducer has also