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

Norbert Bornfeld, Prof. Dr. med.

Department of Ophthalmology, University of Essen Hufelandstrasse 55, D-45122, Essen, Germany

Sarah E. Coupland, MBBS, PhD

School of Cancer Studies, University of Liverpool 5 049, Duncan Building, Daulby Street, Liverpool L69 3GA, UK

Claus Cursiefen, Priv.-Doz. Dr. med.

Department of Ophthalmology, University of Erlangen-Nürnberg, Schwabachanlage 6 D-91054 Erlangen, Germany

Rudolf F. Guthoff, Prof. Dr. med.

Department of Ophthalmology, Rostock University Doberaner Strasse 140, D-18057 Rostock, Germany

Ludwig M. Heindl, Dr. med.

Department of Ophthalmology, University of Erlangen-Nürnberg, Schwabachanlage 6 D-91054 Erlangen, Germany

Leonard M. Holbach, Prof. Dr. med.

Department of Ophthalmology, University of Erlangen-Nürnberg, Schwabachanlage 6 D-91054 Erlangen, Germany

Antonia M. Joussen, Prof. Dr. med.

Department of Ophthalmology, Heinrich-Heine University, Moorenstrasse 5, 40225 Düsseldorf Germany

Anselm Jünemann, Prof. Dr. med.

Department of Ophthalmology, University of Erlangen-Nürnberg, Schwabachanlage 6 D-91054 Erlangen, Germany

Bernd Kirchhof, Prof. Dr. med.

Department of Vitreoretinal Surgery, Center for Ophthalmology, University of Cologne, Joseph- Stelzmann-Strasse 9, D-50931 Cologne, Germany

Friedrich E. Kruse, Prof. Dr. med.

Department of Ophthalmology, University of Erlangen-Nürnberg, Schwabachanlage 6 D-91054 Erlangen, Germany

Christian Y. Mardin, Prof. Dr. med.

Department of Ophthalmology, University of Erlangen-Nürnberg, Schwabachanlage 6 D-91054 Erlangen, Germany

Gottfried O.H. Naumann, Prof. (emer.) Dr. med. Dr. h.c. (mult.)

Department of Ophthalmology, University of Erlangen-Nürnberg, Schwabachanlage 6 D-91054 Erlangen, Germany

Ursula Schlötzer-Schrehardt, Prof. Dr. rer. nat.

Department of Ophthalmology, University of Erlangen-Nürnberg, Schwabachanlage 6 D-91054 Erlangen, Germany

Ernst R. Tamm, Prof. Dr. med.

Department of Anatomy, University of Regensburg Universitätsstrasse 31, D-93053 Regensburg, Germany

G.O.H. Naumann, F.E. Kruse

1.1

Ophthalmic Pathology in Clinical Practice, Teaching and Research

As ophthalmologists we are fascinated by the structures of the normal and diseased eye. The clear optical media allow almost all tissues within the eye to be observed directly in vivo. The interpretation of clinical observations obtained by echographic techniques, fluorescein angiography (FA), optical coherence-laser tomography (OCT), confocal laser scanning in vivo microscopy, polarimetry, etc., requires a precise knowledge and direct correlation with the ophthalmopathologic basis. This is true for quantitative pathology and in vivo “biomorphometry” as well as for quantitative in vivo cytology – “biocytology” – such as corneal endothelial microscopy. Ophthalmic pathology comprises the entire spectrum of structural changes, ranging from slit lamp microscopy and “biocytology” to the available laboratory methods of general pathology including macroscopy, light and electron microscopy, immune histochemistry as well as modern molecular and cell biology. Ophthalmopathology thus offers a three-dimensional framework for morphologic differential diagnosis, and also for the training of medical students and ophthalmologists.

The necessity for clinicopathologic correlations (CPCs) with excised tissues and enucleated eyes is particularly obvious for the following reasons:

1.1.1

Confirmation and Quality Control of Clinical Diagnoses

Confirmation and quality control of clinical diagnoses are indispensable in infectious diseases and oncology for the appropriate therapy. The correction of misdiagnoses is also one of the most effective tools in teaching.

1.1.2

Modern Ophthalmomicrosurgery is Applied Ophthalmopathology

This is no exaggeration, as ophthalmic microsurgery today is done with the same magnifications as for low

light microscopy in the laboratory. In fact, the main purpose of this book is to illustrate this everyday experience. As a prerequisite for the recognition and prevention of potential complications, we can modify the surgical approaches – keeping in mind the vulnerability of the most critical cell populations involved.

We shall not discuss and illustrate the whole spectrum of morphologic elements but confine ourselves mainly to the magnifications of both light microscopy and the operating microscope. We shall illustrate simple stains such as the standard hematoxylin and eosin (HE), and periodic acid–Schiff (PAS), to outline the resistant structures of outstanding basement membranes like Descemet’s and Bruch’s membrane, the inner limiting membrane of the retina, and the lens capsule. The Masson stain facilitates the distinction between epithelial (red) and connective mesenchymal tissue (blue).

Studies of wound healing after ophthalmic microsurgery and its complications in and around the eye are of particular interest – “scar wars” – by being excessive or insufficient.

1.1.3

Ophthalmic Pathology is the Science of the Phenotype

Defining the phenotype in a reproducible fashion therefore has become more important than ever if a meaningful correlation to a genotype is sought. Criteria for the phenotype in ophthalmology rely mainly on morphologic features: Today refined methods for quantification are available, e.g. for measuring corneal endothelial density, size of the optic disc and its intraand peripapillary alterations. And one might add: ophthalmic examination and microsurgery are concerned with the morphologic phenotype. Microsurgical manipulations of the genotype are a topic for the future and might potentially require the appropriate nanotechniques.

1.1.4

Ophthalmic Pathology also Connects Experimental and Clinical Ophthalmology

In view of the very close interrelation between clinical practice and ophthalmic pathology, it is highly desirable that the ophthalmic pathology laboratory should be closely integrated, also geographically, into departments of ophthalmology “in situ.”

Obviously a close cooperation with the general pathologist is necessary and fruitful, especially in the differential diagnosis of orbital processes and peculiar lid alterations.

On the other hand, we know from many consultations with general pathologists that they experience difficulties in the differential diagnoses of conjunctival and even common intraocular diseases. The specific pathology of the “eye” mandates this interdisciplinary exchange and makes it a rewarding experience.

As in all paths of life we need to know the history to better understand the present and also to judge the opportunities and risks of the future.

A very brief sketch of the history of ophthalmic (mi- cro-)surgery may be of interest (Tables 1.1, 1.2).

Table 1.1. Historical overview of ophthalmic surgery from antiquity to 1800

1700 B.C. Codex Hammurabi, Mesopotamia

500 B.C. Susrata, India: cataract couching

25 B.C.– Aulus Cornelius Celsus (25 – 35 A.D.): first descrip50 A.D. tion of cataract couching via the “pars plana ap-

proach”

1163 Council of Tours: “Ecclesia abhorret a sanguine”

1583 George Bartisch, oculist to the Court of Saxony in Dresden: Ophthalmodouleia textbook: enucleation, exenteration, cataract couching, triachiasis, ptosis, blepharochalasis surgery

1750 Jacques Daviel: extracapsular cataract surgery

1793 Ecole Sant´e, Paris: surgery in addition to medicine included in the university curriculum of the Medical Faculty

1.2

Historical Sketch of Ophthalmic Surgery from Antiquity to Modern Times

During the last century (from 1900 to 2000), advances in ocular surgery were more rapid and spectacular than in the entire previous history. The following pioneers and their procedures represent milestones for this period:

1905 Zirm was the first to perform corneal transplantation as the first transplantation in humans. He used the clock-driven trephine developed by Arthur von Hippel 1877.

Table 1.2. Selected overview of ophthalmic surgery after 1800

1839 Johann Friedrich Dieffenbach, Berlin: extraocular muscles/squint surgery

1856 Albrecht von Graefe, Berlin: iridectomy for angle closure glaucoma

1858 George Critchett, London: principle of filtrating surgery

1860 William Bowman, London: optical sector iridectomy for keratoconus inferiorly. Superior location for antiglaucomatous iridectomy

1866 Alexander Pagenstecher, Wiesbaden: intracapsular cataract surgery

1884 Carl Koller, Vienna: local anesthesia with cocaine

1905 Eduard Zirm, Olmütz: successful corneal grafting

(5.0 mm) as the very first successful human tissue transplantation

1916 Jules Gonin, Lausanne: first successful procedure for retinal detachment

1927 Wladimir P. Filatow, Odessa: donor cornea from cadaver

1949 Gerd Meyer-Schwickerath, Essen: light coagulation and light surgery for retinal disease without opening the eye

1949 Harold Ridley, London: pioneer of intraocular lens implant after extracapsular cataract removal with PMMA

1952 Ernst Custodis, Düsseldorf: external implant for retinal detachment

1958 Joaquin Barraquer, Barcelona: erysophake and [ - chymotrypsin for zonulolysis facilitating intracapsular cataract extraction

1956 Tadeusz Krwawicz: intracapsular cryoextraction of cataract

1950/ Heinrich Harms and Gunter Mackensen, Tübingen;

60Joaquim Barraquer, Barcelona; Jörg Draeger, Hans Sautter, Hamburg; et al.: operating microscope for ophthalmic microsurgery

1965 Charles Kelmann, New York: phakoemulsification revolutionizing extracapsular cataract extraction

1965 Jos´e Barraquer, Bogota: mechanical keratomileusis

1969 Robert Machemer, Göttingen, Miami, Durham: pars plana vitrectomy for vitreal and retinal disease

1970 Hugo Hager, Tübingen: laser trabeculoplasty

1975 Trokel and Srinivasan: excimer laser 193 nm – experimental ablation of cornea

1975 Franz Fankhauser, Bern, and Aron-Rosa, Paris: YAG-laser iridotomy and capsulotomy for secondary cataract

1985 Theo Seiler and Josef Wollensak, Berlin: excimerlaser corneal refractive ablation (PRK) in patients

1988 Ioannis Pallikaris, Crete: LASIK

1916 Gonin developed the first cure for retinal detachment.

1949 Ridley started the era of lens implantation.

1949 Meyer-Schwickerath pioneered light coagulation as the precursor of laser medicine.

1952 Custodis proposed episcleral implants for the closure of retinal defects causing retinal detachment.

1956 Kwrawicz initiated cryotherapy in cataract extraction.

1960 Jos´e Barraquer started mechanical refractive surgery of the cornea, and 25 years later, Seiler and Wollensak used photorefractive keratectomy (PRK) to treat myopia.

1969 Robert Machemer opened up a new era in intraocular surgery by devising the “pars plana vitrectomy.”

1975 Fankhauser developed the YAG-laser, opening up a new era in antiglaucomatous iridotomy and in the treatment of secondary cataracts of extracapsular surgery.

Surgery in and around the eye started in antiquity; only a few names can be mentioned (Table 1.1).

The Codex Hammurabi lists the drastic punishments for surgical failures and complications.

Susratra first documented cataract surgery in India in 500 B.C.

During the Council of Tours (1163 A.D.), a Medical Faculty was accepted for the first time in the medieval university, but surgery was excluded because it was considered an ordinary craft: “Ecclesia abhorret a sanguine!”.

Long-term effects are evident to this day: British tradition in medicine still distinguishes between “Mr.” and “Ms.” for surgeons and “Doctor” for conservative physicians. Georg Bartisch, an oculist at the Saxonian Court in Dresden, in 1583 wrote Ophthalmoduleia – the first textbook of ophthalmic surgery – but was not considered a physician. He described procedures for lid processes, extraocular muscles and enucleations. A somewhat condescending arrogant attitude of non-sur- gical medical colleagues towards surgeons can be observed occasionally even in our time. The editors of the

New England Journal of Medicine in January, 2000, in their article “Looking back at the Millennium in Medicine” omit surgery and anesthesia completely – and this is probably not only a different linguistic tradition.

Only after 600 years in 1793 did the Ecole Sant´e, Paris, finally welcome surgery in the Medical Faculty as an academic entity at the European university.

A tabulated overview of the advances in ophthalmic (micro-) surgery in the nineteenth and twentieth centuries outlines some of the spectacular advances made in ophthalmic surgery in the last 200 years. They are highlighted by some of the outstanding pioneers (Table 1.2).

Hermann von Helmholtz, Königsberg (1850), developed the ophthalmoscope (Augenspiegel), allowing the fundus of the eye to be observed for the first time – making visible diseases of the retina. This made dis-

eases of the eye, such as retinal detachments, a goal of therapy.

Albrecht von Graefe in Berlin, Bowman in London, Donders in Utrecht, et al. pioneered modern ophthalmology. In 1856 von Graefe cured acute angle closure glaucomas by iridectomy. George Critchett, London (1858), proposed the principle of filtrating surgery which was later modified by Heine, Holt, Lagrange, Elliot and others.

William Bowman, London, published in 1849 “Lectures on the parts concerned in the operation on the eye.” He performed optical sector iridectomy inferiorly for keratoconus; he also suggested performing iridectomy for acute glaucomas superiorly to be partially covered by the lids (1860).

Eduard Zirm, Olmütz (1905), demonstrated successful corneal grafting 5 mm in diameter as the very first successful human tissue transplantation.

Jules Gonin, Lausanne (1916), proposed the first successful procedure for retinal detachment.

Tsutomu Sato, Tokyo (1930), attempted refractive surgery of the cornea by incisions in Descemet’s membrane.

Gerd Meyer-Schwickerath, Hamburg, Bonn and Essen (1949), pioneered light coagulation and non-me- chanical “light surgery” for retinal diseases without opening the eye. This principle was later enhanced in 1960 by various lasers applied to the anterior and posterior segment of the eye and in all medical specialties (Fig. 1.1).

Harold Ridley, London (1949), first inserted an intraocular lens implant consisting of polymethylmethacrylate (PMMA) into extracapsular aphakic eyes.

Ernst Custodis, Düsseldorf (1952), introduced an external implant for retinal detachment. Arruga and Schepens modified this approach.

Heinrich Harms (1955/1960), Günter Mackensen (Tübingen), Joaquim Barraquer (Barcelona), Jos´e Barraquer (Bogota), Jörg Draeger and Hans Sautter (Hamburg) and other Europeans together with E. Malbran and R. Troutman introduced and perfected the use of the operating microscope and microinstruments within ophthalmic surgery (Fig. 1.2).

Charles Kelman, New York (1965), revolutionized cataract extraction with phakoemulsification.

Hugo Hager, Tübingen (1970), introduced laser trabeculoplasty (which was further developed by Krasnow and Wise in 1976).

Robert Machemer, Göttingen, Miami and Durham (1969ff), developed pars plana vitrectomy a pioneering new treatment of vitreal and retinal diseases, that were considered hopeless. He gave a chance to help patients with massive vitreal hemorrhage from diabetic retinopathy and trauma etc.

Trokel and Srinivasan used a 193-nm excimer laser in the experimental ablation of cornea in rabbits.

Fig. 1.1. Gerd Meyer-Schwickerath, 1920 – 1992, Hamburg, Bonn, Essen, Germany. Pioneer of “light surgery” initially with the “heliostat” using the light of the sun (1949), later with the xenon high pressure lamp. Afterwards modified by laser technology

Fig. 1.3. Lorenz E. Zimmerman (1920–): Chairman, Department of Ophthalmic Pathology, Armed Forces Institute of Pathology, Washington, DC/USA, mentor of a generation of ophthalmic pathologists from around the world

Fig. 1.2. Operating microscope: range of magnification from 6- to 40-fold projected on the eye (modified after Harms and Mackensen 1966)

Franz Fankhauser, Bern, and Aron-Rosa, Paris (1975), performed YAG-laser iridotomy and capsulotomy for secondary cataracts, and carried out non-mechanical and non-thermal intraocular surgery without opening the eye.

1.3

Overview of Advances in Ophthalmic Pathology in the Nineteenth and Twentieth Centuries

Some milestones and personalities in ophthalmic pathology/anatomy are listed to give an indication of how much interest this subject has received despite its small size (Table 1.3).

Rudolph Virchow, Berlin: recognized retinoblastoma, which he termed “glioma” – and uveal melanoma as a malignant tumor.

Theodor Leber, Heidelberg: defined inflammatory processes and angiogenesis in the cornea and coined the term “chemotaxis” (1879).

Ernst Fuchs, Vienna: father of modern ophthalmic

Table 1.3. Milestones and personalities in ophthalmic pathology and anatomy from antiquity to the present

pathology (together with Parsons, London, and Frederic Verhoeff, Boston). He described sympathetic uveitis, and many entities bear his name.

Eugen v. Hippel, Göttingen: phakomatoses (1895). Frederick Verhoeff, Boston: defined “retinoblastoma”

as originating from photoreceptors. Established criteria for so-called “endophthalmitis phacoanaphylactica.”

Karl von Wessely, Munich: immune ring of the cornea. Edited a three-volume textbook on ophthalmic pathology, 1930 – 1938.

Norman Ashton, London (1950ff – 2001): established an experimental model of retinopathia praematurorum based on reactive retinal hypoxia following excess

oxygen exposure. Pioneer of experimental ophthalmic pathology.

Helen Wilder, Washington (1953): identified toxoplasmosis retinochoroiditis and Toxocara canis endophthalmitis in enucleated eyes.

Lorenz E. Zimmerman (Fig. 1.3), Washington (1953ff): “put the house of ophthalmopathology in systematic order” based on morphologic criteria of the phenotype. Created a school of ophthalmic pathology around the world, emphasizing clinicopathologic correlations (CPCs)!

Thaddeus P. Dryja (1990): identified the retinoblastoma suppressor gene.

The principal indications for extraand intraocular surgery are similar to those of surgery for other purposes. However, surgical procedures inside the eye are associated with a unique pattern of complications. They not only affect the site of entry but tissue distant to this location.

Obviously, clinical ophthalmology, ophthalmic pathology and ophthalmic microsurgery share principal approaches in the spectrum of conservative medicine and macrosurgery. The eye requires a different approach from other organs in the body because of: (1) its small dimensions, (2) the delicate structure of the intraocular tissues and, importantly, (3) the fact that the intraocular pressure is significantly higher than the tissue pressure of other organs (Tab. 2.1).

Use of the operating microscope was pioneered by ophthalmologists and has contributed to the spectacular progress not only in microsurgery of the eye but also in other specialties in the last 50 years (see Chapter 1, Sect. 2). The magnification used covers part of the range used in light-microscopic histopathologic study. Approaches for the eye range from morphologic in vivo diagnosis with the slit lamp, A- and B-echography, optical coherence tomography (OCT), ultrasound biomicroscopy, laser in vivo confocal microscopy, ultrasound biomicroscopy (USB) and fluorescence angiography, etc., to observation and action under the operating microscope. Thus either excised tissue or the entire eye can be studied in the ophthalmic pathology laboratory. The surgical anatomy with lines, planes and spaces as landmarks has particular importance for the ophthalmic microsurgeon for orientation; the anatomy for each tissue is discussed under the relevant section.

Table 2.1. Special features of the eye’s normal function

1.Blood-ocular barrier (Fig. 2.6)

2.Avascularity of cornea, anterior chamber, lens and vitreous

3.All vascularized tissues spare the optical axis

4.Increased tissue pressure maintains a smooth refractive surface of the cornea and properly aligned photoreceptors

5.Sensory retina is transparent

Discussions in this book are confined to light microscopic dimensions enhanced by electron microscopy if necessary, e.g., in the pseudoexfoliation syndrome (see Chapter 6.3). “Biocytology” means the non-invasive study of single cells in vivo, e.g., specular microscopy of the corneal endothelium or of individual benign or malignant melanocytes on the surface of the gray-blue iris or the anterior lens capsule.

We shall not discuss proteomics with the imaging of molecules. Nanomedicine on a scale of less than 100 nm may have exciting potential for diagnosis and therapy and will probably demand further sophistication of ophthalmic microsurgery beyond our current imagination. These channels of current interdisciplinary “high risk research” will lead to investigations which will also include and fascinate the ophthalmic microsurgeon and the pathologist. Our current state of knowledge does not allow us to speculate on how these paths will develop in the future.

“Robotic surgery – squeezing into tight places” – making microsurgery “go digital,” may also have great potential for the future. Currently it is good for extirpation but not for reconstruction (Berlinger 2006).

2.1

Principal Indications: Clinico-pathologic Correlation

The principal indications in ophthalmic microsurgery are similar to those in macrosurgery concerning other organs of the body. We shall briefly outline these obvious principal indications.

2.1.1 Defects

Defects in the scleral wall of the globe or in the cornea due to trauma or surgery cause more or less pronounced ocular hypotony. Hemorrhage into the anterior chamber and vitreous from damaged vascularized tissue may be profuse due to the suddenly decreased tissue pressure. Prolonged ocular hypotony always causes uveal effusion followed by progressive choroidal