Ординатура / Офтальмология / Английские материалы / Applied Pathology for Ophthalmic Microsurgeons_Naumann, Holbach, Kruse_2008

5.2.4.8

Concept of a Transtrabecular Shunt Between the Anterior Chamber and Schlemm’s Canal

According to McEwen, one opening alone in the trabecular meshwork of 20 µm would be sufficient to guarantee a normal aqueous outflow. Current methods of “rough” mechanical trabecular surgery probably scar to a considerable degree. They are probably successful only if a remnant of the outflow window with a minimum of 20 µm stays open. Wound healing is probably accelerated by growth factors within the blood leaking into the wound area after mechanical surgery (Table 5.2.10). The currently utopian goal to achieve the above shunt hypothetically could include the use of an ultrashort infrared femtolaser (10–15) using doses in the terawatt range (1012 W). Ideally this infrared femtolaser would overcome the semi-opaque corneoscleral limbal zone transmission zone, starting ablation of the trabecular mesh-

work on the side of the anterior chamber and extending slowly to the level of Schlemm’s canal. This would require preoperative determination of the exact depth of Schlemm’s canal within the corneoscleral region measured by optical coherence tomography (OCT) or ultrasound biomicroscopy (UBM) (Fig. 5.2.17).

5.2.4.9

Transscleral Coagulation of the Ciliary Body

In contrast to the above mentioned procedures, transscleral coagulations aim to partially destroy the aqueous producing non-pigmented ciliary epithelium. Both cryoand diathermic coagulation cannot avoid a coagulation of the adjacent sclera and ciliary muscle – more pronounced with diathermia. For this reason today cyclocoagulation is the preferred method. The transscleral infrared diode laser coagulation of the pars plicata has the principal advantage of avoiding necrotic

changes in the overlying sclera – as well as the risks associated with an opening of the eye (see Chapter 2, Sect. 2) – but as an exception scleral perforation may occur. Coagulation of the pigmented ciliary epithelium is associated with necrosis of the adjacent ciliary muscle (Fig. 5.4.32). Cyclodestructive procedures may pose extra risks in PEX (Zonula! BAB! See Chapter 6.3).

imminent pupillary or ciliary block situation, if the anterior chamber is opened

3.A combination of both trabecular meshwork disease and imminent pupillary block is another possibility (Table 5.2.5)

4.A POAG with a very narrow angle represents only a particularly difficult type of open angle glaucoma (Table 5.2.1 and 5.2.5).

5.2.4.10

Contraindication to Filtering Procedures

Fresh angle closure glaucomas are best treated by YAGlaser iridotomy, if necessary mechanical peripheral iridectomy. Filtering procedures are accompanied by a risk of ciliary block angle closure glaucoma (malignant glaucoma, see below). The same is true for open but narrow angle glaucomas, especially with relative anterior microphthalmus (RAM, Auffarth and Völcker, 2000, 2006).

5.2.5

Complications with Excessive and Deficient Wound Healing

The most important considerations for avoiding complications are:

1.To clearly distinguish between closed angle glaucomas and open angle glaucomas

2.A narrow angle may still be open with the otherwise normal trabecular meshwork; it may be an

5.2.5.1

Acute Postoperative Decompensation of Intraocular Pressure

Complications of filtrating surgery are either an insufficient or excessive wound closure and healing. They are associated with acute postoperative decompensation either down or up:

Defects of wound healing from the conjunctival or corneo-conjunctival wound lead to persisting ocular hypotony, narrowing or flattening of the anterior chamber and detachment of the choroid (see Chapter 2). This situation requires posterior sclerotomy, reformation of the anterior chamber and revision of the conjunctival wound usually within a week – earlier if the lens touches the cornea.

Malignant postoperative ciliary block angle closure with loss of anterior chamber may follow filtrating surgery particularly in eyes with small anterior segments (RAM) showing all the signs of an acute glaucoma. This requires pars plana vitrectomy and/or removal of the lens and reestablishment of the anterior chamber.

Table 5.2.13. Growth factors in wound healing (“scar wars”) (according to P. Khaw): Stimulation of migration, proliferation and collagen synthesis of human Tenon’s capsule fibroblasts

5.2.5.2

Late Conjunctival Bleb Wound Dehiscence

Late conjunctival bleb wound dehiscence can be the precursor of a localized infection or progressive endophthalmitis. Debry et al. (2002) found in a series of 239 eyes, a bleb leak in 8 % and a “blebitis” in 2 % following trabeculectomy with mitomycin with a followup of 2.7 years. Inhibitors of growth factors to prevent scarring of the filtering bleb are insufficiently understood as are the rusulting “scar wars” (according to P. Khaw). The role of cytostatic substances like mitomycin C and/or 5-fluouracil is currently being intensively studied in many institutions around the world. Especially scarring in the tenon’s tissue in relation to preexisting inflammatory infiltrate and growth factors from blood and sclera with conjunctival vessels needs to be considered in future studies of wound healing. Large cystic blebs may extend in front of Bowman’s layer – they can be separated from the cornea by blunt instruments and then reduced in size (Fig. 5.2.16). The role of the corneal endothelial proliferation and migration from the inner opening of filtrating surgery and its extent in the episcleral region requires further study.

5.2.5.3

Failure of Goniotomy

As the procedure originates from the opposite side of the anterior chamber, simple rotation works with twice the radius of Schlemm’s canal. Histopathologic studies show Schlemm’s canal septated and following a variable course. This implies that it is difficult or impossible to maintain the same depth of incision into the structures of the chamber angle. The few globes available for histopathologic study after goniotomy and trabeculotomy often reveal evidence of an atypical cyclodialysis and not the intended shunt from the anterior chamber to Schlemm’s canal over 120° (Fig. 5.2.13).

If Schlemm’s canal is absent, both procedures cannot be performed “lege artis” of course. Correspondingly the results are very poor in these congenital complex anterior segment anomalies.

5.2.5.4

Failure of Filtering Surgery for Chronic Open Angle Glaucoma

Current methods of medical or microsurgical therapy are not satisfactory. Treatment of ocular hypertension is recommended if: (1) the pressure exceeds 30 mm Hg, because of the increased risk of CRVO (see Ch. 5.6) (2) there is definite reproducible threshold damage to the optic disc, defining “early glaucoma,” or (3) there is definite reproducible change (delta) of the optic nerve head during follow-ups including in its interpretation the quantification of the disc area and its juxtapapillary zones (Jonas et al., 1999).

As current approaches by laser or filtering surgery are not yet optimal, treatment is started usually medically. After local therapy for months or years inevitably an iatrogenic chronic conjunctivitis develops with more or less pronounced hyperemia even if preservatives are not included in the eyedrops. This may be a cause of excessive scarring and closure of the filtering channel from episcleral wound healing.

5.2.5.5

Postoperative Peripheral Anterior Synechiae

5.2.5.5.1

Thermic Laser Trabeculoplasty

Thermic trabeculoplasty initiates thermal necrosis of approximately 40 – 50 µm spots around the trabecular meshwork. How this improves – often temporarily – the aqueous outflow in approximately two-thirds of treated patients is not exactly known. It is speculated that the trabecular endothelial cells adjacent to the thermal burn proliferate in the wound healing process and “rejuvenate” the trabecular meshwork. If the placement of the argon laser spot reaches the scleral spur or more posteriorly including the uveal tissue covering the ciliary band focal anterior hairlike synechiae often develop. This posterior application can induce secondary angle closure from confluent argon laser spots. If this occurs in more than one-half the circumference, secondary angle closure glaucoma is the most unpleasant complication.

5.2.5.5.2

Subsequent Filtering Procedures

Postoperatively the anterior chamber may be shallow or absent for a few days. If contact between lens and cornea is seen, immediate intervention to restore the anterior chamber is necessary. The same may be indicated if the anterior chamber does not deepen within a week. Failure to restore the anterior chamber in time may cause persistent anterior synechiae and even secondary angle closure glaucoma. This negates the goal of the procedure.

5.2.5.6

Consequences of Acute and Persistent Ocular Hypotony Following Filtrating Glaucoma Surgery

The hypotony may be the result of wound leak, excessive filtration without wound leak or, rarely, an unintentional atypical cyclodialysis. Regardless of the etiology the consequences are similar. Hyperemia of uveal vessels leads to a detachment of the choroid and ciliary body resulting in a visible “choroidal” effusion. This subacute-chronic process concerns the entire uvea and results mainly from obstruction of the outflow via the vortex veins. It displaces the origin of the zonular fibers anteriorly and induces a subluxation of the lens forward. In eyes with a small anterior segment (RAM) the lens may occlude the ring of the ciliary body and leads to a “malignant” ciliary block acute angle closure glaucoma. This requires immediate attention by a combination of posterior vitrectomy, reformation of the anterior chamber and extracapsular or even intracapsular cataract surgery.

Cystoid maculopathy may occur rather frequently after any opening of the eye, by trauma or microsurgically. This is usually reversible after the intraocular pressure is normalized (see Chapter 2, 4). High resolution OCT has improved our insight in this process.

Expulsive arterial hemorrhage originates from an acute rupture of a ciliary artery at the scleral entry into the choroid. Patients with arterial hypertension and high myopia may be at increased risk for this catastrophic event. Quick closure of the wound in the eye wall and posterior scerotomy 4 mm behind the limbus are attempted to save the eye.

5.2.5.7

Corneal Endothelial Proliferation and Migration After Filtrating Surgery

If the inner opening of the drainage channel reaches anteriorly of Schwalbe’s line the contact inhibition between trabecular and corneoendothelium is not functioning: Therefore the corneal endothelium may proliferate through the canal into the episcleral tissue. This is difficult to prove in surgical specimens but may be a factor in the development of cystic blebs. Alternatively if the anterior chamber is so flat that the Fuchs’ roll is in contact with the corneal endothelium, the barrier of Schwalbe’s line again is not limiting the vagaries of the corneal endothelium leading to a persisting closure of the anterior chamber angle with ensuing secondary angle closure glaucoma.

References (see also p. 379)

Alvarado J, Murphy C, Polansky J, Juster R. Age-related changes in trabecular meshwork cellularity. Invest Ophthalmol Vis Sci 1981; 21: 714 – 727

Auffarth GU, Blum M, Faller U, Tetz MR, Völcker HE. Relative anterior microphthalmos: morphometric analysis and its implications for cataract surgery. Ophthalmology 2000; 107: 1555 – 60

Auffarth GU, Voelcker H-E. Cataract surgery in 79 patients with relative anterior microphthalmus (RAM). A review of anatomy, associated pathology and complications. Klin Monatsbl Augenheilk: 2006;216(6):369

CAT-1520102 Trabeculectomy Study Group, Khaw P, Grehn F, Hollo G, Overton B, Wilson R, Vogel R, Smith Z. A pahse III study of subconjunctival human anti-transforming growth factor beta (2) monoclonal antibody (CAT-152) to prevent scarring after first-time trabeculectomy. Ophthalmology 2007 Oct; 114(10):1822 – 1830

Debry PW, Perkins Trabekelwerk, Heatley G, Kaufmann P, Brumback LC. Incidence of late-onset bleb-related complications following trabeculectomy with mitomycin. Arch Ophthalmol 2002; 120:297 – 300

Grierson I, Howes RC, Wang Q. Age-related changes in the canal of Schlemm. Exp Eye Res 1984; 39: 505 – 512

He M, Foster PJ, Johnson GJ, Khaw PT. Angle-closure glaucoma in East Asia and European people. Different diseases? Eye 2006; 20:3 – 12

Holz HA, Lim MC. Glaucoma lasers: a Review of the Newer Techniques. Curr Opin Ophthalmol 2005; 16:89 – 93

Jonas JB, Budde WM, Panda-Jonas S. Ophthalmoscopic evaluation of the optic nerve head. Surv Ophthalmol 1999; 43:293 – 320

Jonas JB, Budde WM, Lang PJ. Parapapillary atrophy in the chronic open-angle glaucomas. Graefes Arch Clin Exp Ophthalmol 1999; 237: 793 – 9

Karlsberg, AMA Archiv Ophthalmology 1979: 86: 287: Wilmer 29294

Khaw PT, Occleston NL, Schultz G, Grierson I, Sherwood MB, Larkin G. Activation and suppression of fibroblast function. Eye 1994; 8(Pt 2): 188 – 195

Knorr HLJ, Jünemann A, Händel A, Strahwald H, Naumann GOH. Morphometrische und qualitative Veränderungen des Hornhautendothels beim Pseudoexfoliationssyndrom. Fortschr Ophthalmol 1991; 88: 786 – 789

Küchle M, Mardin C, Nguyen NX, Martus P, Naumann GOH. Quantification of Aqueous Melanin Granules in Primary Pigment Dispersion Syndrome. Am J Ophthalmol 1998; 126: 425 – 431

Küchle M, Nguyen NX, Mardin CY, Naumann G.O.H. Effect of neodymium:YAG laser iridotomy on number of aqueous melanin granules in primary pigment dispersion syndrome. Graefes Arch Clin Exp Ophthalmol. 2001 Jul;239(6):411 – 5

Kwong YY, Tham CC, Leung DY, Lam DS. Scleral perforation following diode laser transscleral cyclophotocoagulation. Eye 2006; 20: 1316 – 7

Mardin CY, Küchle M, Nguyen NX, Martus P, Naumann GOH. Quantification of Aqueous Melanin Granules, Intraocular Pressure and Glaucomatous Damage in Primary Pigment Dispersion Syndrome. Ophthalmology 2000; 107: 435 – 440 Quigley HA. New paradigms in the mechanisms and manage-

ment of glaucoma. Eye, 2005; 19:1241 – 1248

Rummelt V, Naumann GOH. Cystic Epithelial Ingrowth after Goniotomy for Congenital Glaucoma. J Glaucoma 1997; 6: 353 – 356

Ruprecht KW, Naumann GOH. Unilateral secondary open-an- gle glaucoma with idiopathically dilated episcleral vessels. Klin Monatsbl Augenheilkd 1984; 184:23 – 27

Schlötzer-Schrehardt U, Naumann GOH. Trabecular meshwork in pseudoexfoliation syndrome with and without open-angle glaucoma. A morphometric, ultrastructural study. Invest Ophthalmol Vis Sci 1995; 36: 1750 – 1764

Until the 1970s the iris was considered a special tissue incapable of wound healing. This is still true for small iridotomies that are flushed by aqueous, eliminating the fibrin scaffold which normally initiates wound healing. However, if the wound edges of the iris are well adapted by at least two sutures, healing of the iris tissue

occurs in a similar fashion to in other tissues except that it takes much longer (see Hinzpeter et al. 1974).

The iris separates the anterior and posterior chamber and has the function of an optic diaphragm (Fig. 5.3.1). The pupil lies slightly inferior nasal to the center of the iris; its diameter varies from 1 to 8 mm. A dis-

crete asymmetry may occur in normal individuals; the average diameter decreases with age. The pupillary margin rests on the anterior lens capsule, causing the “physiologic pupillary resistance” leading to a pulsatile flow of aqueous into the anterior chamber. The iris capillaries are lined by non-fenestrated endothelial cells that are an important component of the blood-aqueous barrier (see Fig. 5.3.2). They contribute to the warming of the aqueous which has been cooled in the retrocorneal region contributing to the “paternoster phenomenon” of cells and melanin granules in the anterior chamber. They also furnish oxygen to the aqueous (Helbig et al., see Chapter 6.3).

5.3.1

Surgical Anatomy

The iris is cone shaped, and the pupillary margin is located more anteriorly than the root. This is more pronounced in hyperopic eyes with a shorter optical axis than in myopic eyes with a longer optical axis. Therefore in hyperopic eyes the anterior chamber is more shallow and the physiological pupillary resistance higher (Fig. 5.3.2).

The anterior border layer of the iris consists of a dense collection of fibroblasts and melanocytes within collagen fibers which extends from the collarette to Fuchs’ roll. In this region the iris is significantly thicker than peripheral to Fuchs’ roll and between the collarette and the pupillary margin. Pores within this layer allow free communication with the aqueous humor. Nests of uveal melanocytes appear as “freckles” and/or the relatively common iris nevi.

Dendritic melanocytes as remnants of the pupillary membrane are often seen on the anterior lens capsule. Using the slit lamp with high magnification (× 40), one can recognize nuclei and uveal melanin granules. Mela- nin-containing macrophages appear on the slit lamp as round corpuscles (Table 5.3.1).

The sphincter pupillae muscle is approximately 1 mm wide and innervated by parasympathic nerve fibers from the oculomotor nerves. The dilator pupillae muscle consists of the myoepithelial portion of the anterior iris epithelium, which is 4 µm thick and extends up around 50 – 60 µm in a radial direction. It is innervated by non-myelinated [ -sympathetic fibers. Alphablocking agents for prostatic hypertrophy, e.g., tamsulosin, therefore as an unintended side effect produce a sluggish iris and a small pupillary diameter, making

a

Table 5.3.1. Iris-pigment epithelium defects on transillumination

cataract surgery more demanding: intraoperative floppy iris syndrome (IFIS); see Chapter 5.5. The iris stroma contains myelinated and non-myelinated nerves originating from the nasociliary nerves via the long and short ciliary nerves of the trigeminus. They account for the pain sensitivity.

The pupillary portion of the iris pigment epithelium moves constantly against the anterior lens capsule. With age these cells lose some of their melanin granules, which are then distributed in the aqueous and phagocytized by the corneal and trabecular endothelium. The blood supply of the iris is characterized by many anastomoses. The incomplete major circle of the iris is present in the iris root, arriving from the anterior loops of the anterior ciliary artery branches. An incomplete minor arterial circle runs parallel to the collarette.

The iris root peripheral to Fuchs’ roll is only 25 – 50 % as thick as the central iris stroma. Its basal portions continue to the face of the ciliary body. Laser iridotomy should best be focused here preferably in the “stretched” iris associated with a pupil contracted by miotic drops such as pilocarpine.

5.3.1.1 Blood-Aqueous Barrier

In the iris the blood-aqueous barrier is based in the non-fenestrated endothelial lining of the capillaries surrounded by a thick collagenous sheath (see Fig. 2.1; and 2.6).

Congenital anomalies of the pupil are rare (Fig. 5.3.3). Congenital adhesions of the iris develop as part of the anterior cleavage syndrome (Fig 5.3.4).

Fig. 5.3.3. Congenital anomalies and acquired deformation of the pupil. a Normal. b Aniridia. c Corectopia. d Multicoria. e Multiple posterior synechiae inhibit dilatation of the pupil. f Anterior synechiae from the iris to cornea after stab trauma

a

b

c

d

Fig. 5.3.4. Congenital anomalies of anterior uvea and cornea as a spectrum of the anterior chamber cleavage syndrome. a Prominent Schwalbe’s rim. b Axenfeld anomaly. c Rieger’s anomaly. d Peters’ anomaly

5.3.2

Surgical Pathology

5.3.2.1

“Biocytology” of Minimal Microsurgical Trauma

The uveal melanocytes of the stroma and the iris pigment epithelium are particularly vulnerable to microsurgical trauma by mechanical instruments, e.g., forceps and scissors, and/also by thermic argon or YAG-la- ser application. The collarette is exposed to very peripheral fundus-thermal-laser coagulation via threemirror contact lens particularly if the pupil is dilating poorly. High magnification allows one to differentiate between the pigmented cell populations of the iris, particularly in patients who have a blue or gray iris (Table 5.3.2).

Any microsurgical trauma may lead to focal necrosis surrounded by a zone of depigmentation, visible melanophages and/or proliferation of the pigment epithelium often induce posterior synechiae. This is always associated with a circumscribed temporary breakdown of the blood-aqueous barrier which can be quantified by laser tyndallometry.

If the iris dilates poorly, e.g., in diabetic and pseudoexfoliation syndrome (PEX) iridopathy or with age,

Table 5.3.2. Iris-stroma necrosis: differential diagnosis

1. Congenital: Rieger’s anomaly

2. Acquired: Ischemic infarct: angle closure glaucoma Anterior segment necrosis after encircling episcleral “retinal” implant

Ischemic ophthalmopathy with carotid artery occlusion

Thermic laser burns of iris colarette during laser coagulation of peripheral fundus

Iridoschisis and ICE syndrome PEX iridopathy

Xeroderma pigmentosum

treatment of the peripheral fundus by thermic lasers may accidentally burn the edges of the collarette and lead to a peculiar superficial stroma necrosis (Fig. 5.3.5). Melanophages contain melanin from destroyed uveal melanocytes and/or pigment epithelium.

5.3.2.2

Melanin Dispersion from the Iris Pigment Epithelium

Liberation of melanin granules from the iris may be caused by: (1) blunt trauma, (2) penetrating trauma,

(3) diffuse or sectorial necrosis, e.g., herpetic keratouveitis, (4) diabetic iridopathy, (5) PEX iridopathy involving the epithelium (see Fig. 5.3.6), (6) ischemic sector necrosis of the iris following angle closure glaucoma via pupillary or ciliary block, or (7) spontaneous or induced necrosis of uveal malignant melanomas (Table 5.3.2). Melanin is not the only intraocular pigment (Table 5.3.11).

5.3.2.3

Rubeosis Iridis Followed by Secondary Open and Angle Closure Glaucomas (Figs. 5.3.7, 5.3.8)

Hypoxic and ischemic processes of the retina induce capillary neovascularization of the anterior surface of the iris and angle leading to corneal endothelial proliferation and migration and open angle glaucoma. In later stages angle closure glaucomas develop by progressive contraction of the fibrovascular layer. The pseudoangle then is covered by migrating and proliferating corneal endothelium creating a basement membrane in continuity with Descemet’s membrane (Fig. 5.3.7, Table 5.3.3). Laser coagulation of the ischemic retina may reduce the blood flow through the newly formed capillaries and decrease the breakdown in blood-aqueous barrier. However, the newly formed vessels will not regress after a capillary basement

Fig. 5.3.7. Diabetic iridopathy: a Marked vacuolation of iris pigment epithelial layers by intracellular glycogen (GL) accumulation (lost in fixation) with massive rubeosis iridis: newly formed capillaries (arrows). Iris stroma vessels with collagen mantle (IC), dilator muscle (DM). b Massive splitting of iris pigment epithelial layer by glycogen accumulation in poorly controlled diabetes mellitus forming schisis-like space (M). c Ectropium uvea (EU), rubeosis iridis with anterior synechiae and corneal endothelial migration and proliferation forming pseudoangle (broad arrow), Schwalbe’s line (SL, small arrow)

a

b

c