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Hist Ophthal Intern 2015,1: 139-152
ELUSIVE AGEING MACULA DISORDER (AMD)1
EVOLUTION OF OUR UNDERSTANDING AND ITS NOMENCLATURE
Paulus T.V.M. de Jong
There are inconsistencies in the literature dealing with the layers and tissues of the eye which may be linked to ageing
macula disorder (AMD). Thus, the first aim of this overview is to describe what could be found in the primary historical
literature on these tissues, and what older researchers considered to be their functions. Changes in these tissues asso-
ciated with ageing, sometimes recognized long before the AMD concept was formulated, are then discussed. The earliest
accounts of AMD, using a different terminology, appeared in 1855 and 1868, and linked the presence of drusen with vi-
sual loss. It took a century before these connections between drusen and AMD were generally accepted according to
clinical articles. Finally, the wide variation in AMD nomenclature over the last 160 years, which reflects the uncertainty
of researchers about the causes of AMD up to the present-day, is reviewed.
PubMed and Medline searches were performed for Senile Macular Degeneration, Junius Kuhnt disease, and AMD in
its various meanings in connection with the retina. The bulk of the literature was traced back examining old articles
and, wherever possible, to the original publication date. All manuscripts in the reference list may be obtained from
the author, unless protected by copyright
The author has no conflict of interest.
Introduction. Therefore the first aim of this paper is to ex –
am ine, whe re pos si ble, the earliest available
When thinking about the role of (medical) des crip t ions of the tis sues involved with
history in our studies, we might bear in mind AMD. Second ly, views about their func tion,
that the very words and even letters that we and the morph ological changes in these tis-
read at this moment, are traces of history. Re- sues associated with AMD while ageing, will
searching the literature is, in fact, an act of be examined without writing simply another
historical exploration. Viewing newly discov- review on the patho genesis or treat ment of
ered data in the light of history enables us to AMD.(1,2) The first publications indicating
place our knowledge in perspective. It opens AMD spring from 160 years ago. Although
a broader horizon, yields new insights and drusen were associ ated with visual loss from
makes us view our own achieve ments in a the start, it took over a century before this
more balanced way. Our knowledge of ageing was gene r al ly accepted by medical science.
macula disorder (AMD) has markedly in- Next, changes in AMD termi nology since the
creased over the last 50 years in tandem with first publications will be dis cus sed, revealing
a growing interest in this disorder, partly due the uncertainty of researchers about the
to its increased prevalence in populations pathophysiology of AMD, and even whe ther
with a higher life expectancy. -At the end of AMD is one single disorder or a combination
this paper an explana tion is given as to why of several.
the term ageing ma cu la disor der is preferred
to age-related macular degen er a tion (both Original descriptions of tissues associ-
AMD)-. While research ing AMD, however, ated with AMD and their morphological
marked inac curacies in second ary texts refer- changes, from the sclera towards the
ring to original writings were encountered. inner retina.
Paulus T.V.M. de Jong, MD, PhD, FARVO, FEBOphth,
FRCOphth, Emeritus Professor The earliest known image of the eye and its
Netherlands Institute of Neuroscience, Department of wall was made by Demo critus of Abdera,
Retinal signal processing, KNAW, Meibergdreef 47, around 400 BC. It con tained the more spongy
1105 BA Amsterdam, The Netherlands. tunic, the choroid, which probably means
Department of Ophthalmology, Academic Medical Cen-
that the retina was still unknown at that
Department of Ophthalmology, Leiden University Me- time.(3) The name χιτων χοροειδης “tunic like
dical Center, Leiden a chorion” appears for the first time in Celsus
E-mail: email@example.com Tel +31205666101
1Partly presented at the 28th meeting of the Julius Hirschberg Gesellschaft, Bonn, Germany, October 4 2014, and partly
at the joint Cogan – Hirschberg Society meeting, New York, USA March 28 2015.
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at the start of the common era.(3) The human disci form macular degen er ation (dMD) had
choroid adheres to the sclera with a lamina rup tu res in BrM which were cros sed by new
fusca (dark brown layer), a loose cellular tis- vessels.(1) So for about 80 years people knew
sue with elongated pigment cells.(4) Edmé that changes in BrM were associated with
Mariotte, who described the blind spot in AMD. Only recent ly, three types of mul ti –
1668, erroneously thought that it was created laminar sub-RPE hyperreflect iv ity were de-
by the lack of the light-sensitive choroi dal tis- tected with optical coher ence to mo graphy in
sue on the optic disc.(5) The choroidal layer is the inner, the outer, or both layers of BrM, in
customary divided into the large vessel layer eyes with regressing drusen.(15)
of Haller, the smaller ves sel layer of Sattler,
and the chorio ca pil laris. Duke-Elder consid- The retinal pigment epithelium (RPE)
ered Bruch’s membrane (BrM) to be part of
the choroid.(6) Carlo Mondini mentioned in 1791 a real net-
shaped membrane composed of numerous
In 1722, 40 years before Haller, Fred- inter link ed, black globules.(16) He also wrote
erick Ruysch had published draw ings of that Malpighitold Valsalva that the inner side
choroidal casts, his son named the vascular of the choroid was lined by small black glo –
tunic after his father, and Ruysch’s tunic bules. Mondini already thought that the pig-
seems to have inclu ded the retin al pigment ment served to dampen stray light rays and
epithelium (RPE), BrM, the cho rio ca pil laris, to attach the retina to the pigment layer.
(the ta pe tum) and the choroid.(7,8) His son Francesco added that the pig ment ed
Accor ding to Daniel Esch richt (9) who coin ed globul es were polygonal, that there were no
the name cho rio capilla ris, Hovius (10) was the blood ves sels between this pigmented layer
first to des cribe the chorio ca pil la ris. In the and the retina, and that the black pigment
translation of Hovius’ Latin text, however, I possibly was iron oxide because it was heavier
encountered no clear descrip tion of a capil- than water and was attract ed by a magnet.(17)
lary lay er or membra ne. Around 1820 Jacob con fused many authors
Satt ler men tioned in 1878 nine cho roidal lay- by referring to a mem brane un der the retina,
ers and for unknown reasons the middle layer running from the optic nerve to the cili ary
of the choroid with the larg est blood vessels processes,(18) leading to a “tiring dis cus –
is named after him.(11) sion”.(9)
With advancing age the choroid, including On re-reading Jacob, one has no idea what he
the choriocapillaris, becomes thinner in ma – meant, although Bid der thought that Ja cob’s
cu lae with or without signs of AMD. In mem brane was the rod layer of the retina.(19)
neonates its thickness is 0.15-0.3mm, in In the first description of the RPE as “the
adults 0.1mm.(12) In very old people the reduc- mem brane of the pigment” hexagonal cells
tion in choroidal thickness is 57% compared were mention ed that were circu lar in the
with the youngest age group.(13) human fetus and in albino animals.(20) Bruch
also elaborat ely des crib ed the RPE and was
Bruch’s membrane (BrM) struck by its mono layer and regular, hexa –
gonal shape.(4) He pointed out that the cones
Carl Bruch described this membrane, which were stand ing directly on the RPE cells with-
was named after him, in 1844 in his mono- out any membrane or struc ture be tween
graph on gra nular pigments in vertebrates.(4) them, and that they had a pigment sheath.(4)
BrM is an extracellular matrix be tween the Frans Donders men tioned in 1855 RPE atro-
chorio capil laris and the RPE. Bruch wrote phy be tween groups of drusen.(21) It gradually
that Eschricht described six years earlier this became clear that the RPE could become
mem bra ne in the seal.(4) Esch richt actually hyper tro phied and after fibrous meta plasia
mentioned an extremely thin, serous mem – could con tribute to fibrous tissue in disciform
brane be tween the cho riocapillaris and the lesions. (1, 2, 22, 23)
retina (Table 1, p.141), so BrM should have been Basal laminar or basal linear deposits be-
called Eschricht’s membrane.(9) Ear ly re- tween the cell membrane and the basement
searchers no tic ed that BrM becomes thicker mem brane of the RPE, are often present be-
around age 70 years.(14) It thick ens over time fore drusen appear. These terms were not
by 135% whether signs of AMD are present used in the ori gin al elec tron microscopic des –
or not.(13) Histolog ically, half of 13 eyes with cript ions of these deposits.(24)
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Various names for Bruch’s membrane
Year Author Original name English translation
1838 Esricht (9) Seröser Haut Serous skin, membrane
1844 Bruch (4) Zarte, glashelle, structurlose Membran Soft, structureless membrane, clear as glass
1854 Müller (14) Glaslamelle der Chorioidea; Choroidal glass lamella;
Structurlose Lamelle an der Innenfläche der Chorioidea Structureless lamella on the choroidal inner
1871 Rudnew (32) Glaskörper der Choroides Vitreous body of the choroid
1874 Hutchinson (47) Lamina elastica of the superficial structures
of the choroid
1884 Masselon (30) Membrane (couche) vitreuse de la choroïde Glasslike membrane (layer) of the choroid
1915 Axenfeld (22) Lamina vitrea Glass layer
Drusen of the vitreous membrane of the choroid.
Haab wrote: These drusen, also a change in old age,
have nothing to do with the macular disorder depicted
here (fig.1a) and should be distinctly separated from
Images of senile macular disease.(27)
a b Macula of right and left eye from a 70 year old per-
son; 2. No legend given. 3. a Beginning signs of disease;
3.b 6 months later; 4. a b Right and left eye from a 74
year old female.
Don Gass called them “eosinophilic material
be tween an irreg ul ar ly thick ened BrM and
over lying degenerated RPE.”(23)
Shortly afterwards Shirley Sarks identified in
1970 three types of depo sits(25) and it seems
that she coined the term basal linear de-
Figure 1a posit.(26)
Drusen are now considered to be one of the
hallmarks of AMD but this connection was
explicitly denied by Haab who first described
senile Macular Disease (MD) (Fig.1).(27)
Around 1850, three authors, Wedl,
Donders, and Müller, gave drusen different
labels (Table 2). Carl Wedl named them colloid
bodies of the choroid and thought they were
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Various names for drusen
Year Author Original name English translation?
1854 Wedl (28) Colloidkörper von der Colloid bodies of the choroid
1855 Donders (21) Colloidkugeln Colloid balls
1856 Müller (14) kugelig-drusigen Körper; Ballshaped, drusenoid bodies; druse
1868 Nagel (50) Krystalle; Krystalldrusen Crystals; crystal drusen
1874 Hutchinson (47) “colloid” excrescences from the
1875 Nagel (51) glashäutige Wucherungen proliferations of the glass membrane
1884 Masselon (30) Excroissances verruqueuses Warty growths of the choroid
de la choroïde
1896 Oeller (86) Verrucae laminae vitreae warts of the glass membrane
incompletely developed cells, because they
had no cell membrane or nucleus.(28) Don ders
called them colloid balls surrounded by pig –
ment, noting their prefer en ce for the macular
area. He used around 10 acids and lye’s at
various temperatures, even boiling them to
determine their compos ition, thus being one
of the first his to chemists. He described the Fig. 2a
growth and confluence of the drusen and con – Inferred asso-
cluded that dru sen orig in ate from RPE cell
nuclei.(21) Heinrich Müller mentioned de- glaucoma with
posits on the inner side of the choroid that total disc cup-
had a ball-shaped or dru senoid form. Later in ping and cir-
this paper from 1856 he coined the word cumpapillary
“dru se”.(14) Druse is the Ger man word for
geode, a cavity in rock filled with crystals,
and Müller pro bably chose this name be cause
of the crystalline core in some large dru sen.(29)
Müller wrote that drusen originate behind
the RPE and arise from focal thick enings in
the structureless layer on the inner side of
La ter, the theory was formulat ed that drusen
origin ate from leu co cytes.(32) Around 1884
drusen were even considered to be the cause Fig. 2b
of “posterieur” glaucoma because drusen Drusen and pig-
usually were located around the optic disc. changes in the
This lead to the assumption that thickening fundus.
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of the glasslike layer around the choroidal authors suggested that the retinal vessels
ring hampered the outflow of ocular fluid. might simulate a net. The word retina was
This view was supported by the fact that coined around 1150 AD by Gerardus Cremo –
drusen as well as glaucoma normally were nen sis in a mediaeval Latin trans la tion of an
present in both eyes of old persons (Fig. 2)!(30) Ara bic text.(35) Felix Platter indicated in 1583
Over the years several subtypes of drusen that the retina and not the lens was the light-
were discovered, one of the latest being retic- sensitive organ in the eye.(36) Near ly 100 years
ular, cuticular or pseudodrusen.(31) later, a discov erer of the microscope, An to ny
It is striking that 160 odd years on, van Leeuw enhoek, referred to “cloot gens” at
we still do not know where exactly drusen the end of the fibers of the optic nerve spread –
ori gin ate from. The latest can di date again is ing in the eye, that trans mitted visi ble objects
the RPE, as Donders suggested.(21, 33) to the brain.(37) He used in Dutch the word
“cloot gens” both to indicate cells and fat glob –
The retina. ules. The English trans lation of “cloot gens”
Hippocratesnamed around 350 BC the retina as simply “glob ul es” may have blurred this
το αραχνοειδες (to arachnoeides; the cobweb- dis tinct ion.(37) The photo receptors were
like tunic). This was later changed in rediscover ed 150 years later (Fig 3).(38)
αμφιβληστροειδησ (amfibles tron-like) by- In 1839 Bidder depicted rods and
Herophilus.(3) Am fi blestron at that time had cones in the chicken and men tioned that the
rods were not orien t ed towards the light (the
cornea) but towards the RPE.(19) Albert Kölli –
ker was the first to des cribe the rods and
cones in the human eye as two types of pho-
toreceptors.(39) Only re cent ly, new photosen-
sitive ganglion cells were discov er ed in the
retina, which drive the circa dian clock via the
In 1782 Francesco Buzzi described the ma cu –
la lutea after dis sect ing the eyes of a 35 year
old man in the following terms: Thus in a
point lateral to the optic nerve, also in a heal –
thy condition, one may often see that the
retina is co lor ed yellow, be it rather vague.(41)
Samuel von Sömme ring thought in
1796 that the macula was a hole in the central
retina sur round ed by a yellow ring,(42) but
soon afterwards it was mentioned that the
macula was just a thin spot in the retina.(43-45)
Georges Cuvier men tion ed that the
macula had no color in the neonate but was
b yellow in the adult.(43) The exact size of the
macula was a matter of long discussion and
the area of the central fovea was cal cu la ted
Images of retinal photoreceptors.
to be 0.12mm2 according to its capillary-free
a. Medullar cylinders in rabbit retina.(82) zone.(46)
abba: side view with venous vessels showing through
bccb: oblique section through cylinders
cddc: protruding papillae The pathogenetic process underlying
AMD is still not clear, nor the tissue primarily
b. Photoreceptors of a pike.(38) involved in it. It seems generally accept ed
that thickening of BrM and drusen formation
seven meanings and it is unclear why the in BrM and the RPE, as well as RPE detach-
trans lation “casting net” was privileged over ments and subretinal hemor rha ges pre cede
the other meanings such as “encircling wall” retinal changes of a sec ondary nature like
or “bond” (of the vitreous) (34) be it that some photoreceptor loss or scarring.(1,47)
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for histology. In 1855 after examining 38 ap-
parently healthy eyes he wrote: “An impor-
tant question is in how far the degen er ation
described here (in the retina), can lead to vi-
sual disturbances.”(21) Using microscopy he
noticed rods, oblique ly orient ed around small
drusen as well as degener ation of the cho rio –
capil laris and the RPE. On the choroidal side
of the retina rods and cones often were ab-
sent above drusen, that sometimes pene-
trated the retina halfway, without expanding
the retina on the vitreous side. Drusen com-
pressed the retina (Fig. 5) and rarely were ab-
sent in the eyes of persons aged 70 to 80
years. In none of the eyes he examined post
First colour images ever of the eye fundus(49) from the
thesis by Van Trigt.(83)
Large drusen pressing against the retina ( c ).(21)
aa is choroid, b probably Bruch’s membrane, c retina in
Understanding AMD as a disease entity which drusen protrude
over the years in the light of changing
mort em, had the visual acuity been carefully
re cor ded be fore death. However, he consid-
As a lecturer in physiology, Donders hardly ered that the ana tom ical relation of the
earned enough money to support his family. drusen to the retina and the degen eration of
He agreed to trans late Ruete’s Textbook of the RPE had to have an influence on the reti-
Ophthalmology from German in Dutch while nal func tion. He con clu ded that it would be
moon lighting, and thus beca me interested in rash to pre dict what these colloid changes
ophthalmology. Donders asked his friend would look like using ophthalmo sco py but
Hermann von Helmholtz, who publish ed the was convinced that the white flecks that he
design of the ophthalmoscope in 1851,(48) to had seen sev eral times in the eyes of old peo-
have this ophthalmo scope sent to him. ple suffering from “sen ile am bly opia” (as loss
Hemholtz’ instrument maker could not cope of visual acuity in the elderly was called at
with the many orders, so Donders designed that time) were not fatty meta mor pho ses but
an improved oph thalmoscope and had it colloid degener at ions.(21) An enviable clinical
made by Epkens in Amsterdam. Already in insight!
1853 Donders’ PhD student Adrien van Trigt
wrote a thesis on ophthalmoscopy in which Albrecht Nagel was probably the first
the first world-wide colour images of the fun – to publish on AMD, using both clinical and
dus ap peared (Fig.4).(49) In his early medical histol og ical data from the same patient.(50) In
career Donders performed many autopsies. 1868 he published on a 64 year old woman
From 1852 on, he realized the gap in under – with a dark-red net and partly con fluent
stan ding between what he saw using the oph- white flecks around both maculae who com-
thalmoscope and the mi cro scope. So he plained about marked “ambly opia,” meta –
started collecting “healthy” post mortem eyes morph opsia, and a quiv ering image. Fine
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Nomenclature of ageing macula disorder (AMD) from its very beginning. †
Year Author Original nomenclature English (translation)
1855 Donders(21) Entartung der Chorio-capillaris und Degeneration of the choriocapillaris and
der Pigmentschicht; Amblyopia senilis the pigment layer; senile amblyopia
1868 Nagel(50) Über chorioiditis areolaris und über On areolar choroiditis and on crystals in
Krystalle im Augenhintergrunde the ocular background
1874 Hutchinson(47) Symmetrical central choroido-retinal
disease occurring in senile persons;
Tay’s central guttate choroiditis(49)
1875 Nagel(51) Hochgradige Amblyopie, bedingt durch Advanced amblyopia caused by proliferations
glashäutige Wucherungen und krystal- on the glass membrane and crystalline lime
linische Kalkablagerungen an der In- deposits on the choroidal inner face
nenfläche der Aderhaut;
1875 Pagenstecher(59) Chorioido-Retinitis in Regione Maculae Chorioretinitis in the region of the macula
1878 Michel(61) Ueber Geschwülste des Uvealtractus On tumors of the uveal tract
1884 Nettleship(57) Central senile areolar choroidal atrophy
1884 Nettleship(56) Central guttate choroiditis
1884 Masselon(30) Infiltration vitré de la rétine vitreous retinal infiltration
1885 Haab(65) Erkrankungen der Macula Lutea; Diseases of the macula lutea; senile macular
senile Maculaerkrankung; disease
1887 Goldzieher(58) Ueber die Hutchingsonse Veränderung On Hutchinsonian changes in the posterior
des Augenhintergrundes pole of the eye
1888 Haab(66) Ueber die Erkrankung der Macula On disease of the macula lutea; Senile macular
lutea. Senile Macula-Erkrankung; disease
1892 Caspar(85) Senile Degeneration in der Gegend Senile degeneration in the region of the
der macula lutea macula lutea
Oeller(86) Chorio-Retinitis centralis. Central chorioretinitis. Arteriovenous
Anastomosis arterio-venosa; anastomosis
1893 Fuchs(67) Retinitis circinata Circinate retinitis
1897 Goldzieher(58) Hutchinson‘sche Veränderung des (Hutchinsonian change of the eye fundus.
Augenhintergrundes (Retinitis Fuchs’circinate retinitis )
1897 Walker(62) new growth in the macular region
1899 Silcock(60) Choroidal gumma
1899 Yarr(87) Central choroido-retinitis resembling an
† Only the first time a certain concept was encountered is given here, unless for different (historical) reasons.
Continued next page
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1903 Jessop (63) Tumour in region of yellow spot
1903 Oeller 86 Degeneratio maculae luteae disciformis; Disciform macular degeneration_
1904 Batten(70) Peculiar symmetrical swellings in the macular
1905 Possek(71) senile Maculaveränderung bei Arteriosklerose; senile macular change in arteriosclerosis
1911 Lawford(88) subretinal new growth of doubtful nature
1912 Mosso(74) Degenerazione disziforme della Macula; Disciform degeneration of the macula
1913 Heinrici(89) Degeneratio circinata retinae (Ret. circinata Fuchs) retinal circinate degeneration (Fuchs’circinate
1915 Axenfeld(22) Retinitis externa exsudativa External exudative retinitis
1915 Van der Hoeve(69) Retinitis exsudativa externa External exudative retinitis
1916 Hegner(90) Retinitis exsudativa Exudative retinitis
1919 Elschnig(64) Tumorähnliche Gewebswucherung in der Macula Tumor-like tissue proliferation in the macula
1920 Nöthen H(91) Tumoren in der Maculagegend; Retinitis exsuda- Tumors in the macular region; exudative hemor-
tiva haemorrhagica Coats; rhagic retinitis of Coats
1923 Coppez H(72) Rétinite exsudative maculaire sénile Senile exudative macular retinitis
1926 Junius, Kuhnt(75) Die scheibenförmige Entartung der Netzhautmitte Disciform degeneration of the retinal center (
(Degeneratio maculae luteae disciformis) Scheiben- Disciform macular degeneration) Disciform
1926 Fuchs’ Salzmann(29) senile Makuladegeneration;zentrale senile Senile macular degeneration; central senile cho-
förmige Erkrankung der Netzhautmitte disease of the retinal center
1937 Verhoeff(1) Senile disciform degeneration of the macula
1944 Laird(92) Senile macular degeneration
1959 Maumenee(93) Serous and hemorrhagic disciform detachment
of the macula
1966 Duke-Elder(76) Senile macular degeneration; Senile macular
chorioretinal degeneration; Senile macular dege-
neration of Haab; Senile disciform degeneration
of the macula of Junius and Kuhnt
1967 Gass(23) Disciform detachment of the neuroepithelium;
Senile disciform macular detachment; Senile
macular degeneration; Senile macular choroidal
1969 Straub(77) Altersbedingte Maculadegeneration; Age-determined macular degeneration
1977 Wessing(94) Exsudatieve senile Makulopathie Exudative senile maculopathy
1985 Folk(95) Aging macular degeneration
1987 Sunness(78) Age-related macular degeneration
1992 Klein(96) Age-related maculopathy
1996 Holz(97) Altersabhängige Makuladegeneration Age-dependent macular degeneration
1997 Paglianni(98) Age-related macular disease
2004 De Jong(99) Ageing macular disease
2006 De Jong(80) Aging macula disorder
2014 Camelo(79) Autoimmune macular disease
———————– Page 9———————–
brilliant specks were present, creating the tion of the blood. Es sent ially he thus had al –
impres sion of „Krystalldrusen.“ In 1874 the ready described the present-day paradigm of
patient complained about more metamor- the clinical course from drusen to late AMD.
phopsia. This involved, for instance, human His first three cases dealt with a family, in
legs appearing bent. Nagel pub lished again which three sisters who had experienced the
on this case and two mo re in 1875.(51) The vi- onset of disease at the ages of 40, 48, and 57
sual fields of these patients were normal and years.(47) While reading his account, one won-
the eyes were never pain ful or inflamed. His ders whether they perhaps had suffered from
first patient died at age 73 due to an abdom- Doyne’s honey comb retinal dystro phy, given
inal tu mor; the eyes were enucle ated 27 the rather early age of onset and the fact that
hours post mortem and one was put in there were other cases with visual loss in the
Müllers fixa tive. In the non-fixated eye, there
were small, sparkling irregul arities in the
posterior pole on the inner side of the chor –
oid. They con tain ed hard grains with a diam-
eter up to ½ mm that crun ched under the tip
of a knife. They were mark edly similar to the
whitish crystal-like drusen seen on ophthal –
mo sco py. Nagel conclud ed that the crys talline
mass con sis ted of carbonic acid lime. When
the fixated eye was examined one year later,
no trace of the crys talline drusen, revealed by
ophthal mo scopy, could be found any more
due to dissolu tion in the fixative. On mi-
croscopy, lighter round flecks, surrounded by
a black pigment ring were seen in the RPE.
The flecks were created by thickenings of the Figure 6a (56)
Central guttate choroiditis.
elastic layer where the dis solved drusen had
been and the outer retinal layer over them
was mar ked ly thinner. Nagel thought that
this could explain the metamorphopsia and
ambly o pia the patient complained of.
Nomenclature of AMD from 1855 on-
Table 3, (p.145-146) lists the huge variety of
terms which have been applied to what was
pro bably AMD dur ing the last 160 years.
Only those that seem relevant, either because
of their first or widespread use or the patho –
physiologic con cept they in di cate, will be
In 1874, Jonathan Hutchinson de-
scribed a cho roid, “speckl ed with minute dots
of yellowish white depo sits.“(47) He considered Figure 6b (57)
Central senile areolar choroidal atrophy.
the spots to be “colloid ex cres cen ces of the
lamina elastica” and wrote: “There is no
doubt that the disease is confined to the family. The answer is yes.(52) Doyne, by the
choroid in the first instance, while the great way, did not mention any age in his case re –
de fect of sight which accompanies it points to port.(53) Hutchinson ended his ac count by
im pli cation of the retina se condarily.” He mention ing that his friend Mr Waren Tay
formul ated three stages in the disease: 1. “made the ophthalmoscopic examination,
Scattered yel low-white spots; 2. Coalescence and drew my attention to the peculiarities
of these to pat ches with irreg ular bor ders; 3. present ed.” So should Tay be credited with
Hemorrhage at the yellow spot and absorp- two epony mal disorders? Indeed; apart from
———————– Page 10———————–
Tay-Sachs disease, Tay’s central guttate the fo vea,(67) precip itated an avalanche of
choroiditis was one of the many names for over 50 papers on this topic.(54, 68, 69) Circi nate
Doyne’s dystrophy.(54) Of Hutchinson’s degen er ation (68) or senile exud a t ive retinitis
remain ing cases, five were over age 60, one were proposed as more precise terms.(69) A re –
was 48 and another 38. Thus it seems that view on 61 out of 129 eyes with dMD ha ving
they were not all AMD cases ac cording to our white spots, showed that 36% had circinate
present, rather arbi trary age limit of above reti ni tis.(1) In 1904, 30 years after Hutchin-
50 years.(55) By the way, this naming central son’s paper, sub re tinal hem or rha ges in AMD
guttate choroiditis by Duke Elder was confus- came again to the attention of research ers(70)
ing because Nettleship already mentioned in and one year later athe ro sclerosis was sug –
1884 central guttate choroiditis in a 41 year ges ted as a possible cause.(71) Also fibrous
old woman with a plate that clearly showed plaques in the macular area of old persons, in
drusen, so what we now would name early con junction with punc ta te yellowish dots, fol-
AMD (Fig. 6a).(56) He also published in the same lowed by hemor rhages, were drawn and de-
year on central senile areolar choroidal atro- scribed as senile exud a tive macular
phy, probably now called dry late AMD retinitis.(72)
In the legend which accompanies the
Soon after wards, AMD was referred image of the eye of a 79 year old man from Jo-
to as “Hutchin sonian chang es of the poste- hann Oeller’s atlas (Fig. 7), the word “disci-
rior pole of the eye.”(58) Wilhelm Goldzieher form” appears to have been used for the first
reported on four eyes of unspecified age with
drusen-shaped flecks around the macu la, and
assu med that the changes were due to
atheroma tosis. Unlike Hut chin son he did not
consider these changes a choroidal dis order,
nor col loid ex cres cences of the vitreous
membra ne of the chor oid, but compared
them with cere bral leuko ma lacia caused by
occlus ions of the macular ar ter ioles.(58) In
subsequent years, diag no ses such as chorio –
reti n i tis,(59) sy philis (60) or tumors (61-64) most
likely were referring to AMD.
Although Edward Net tleship had al-
ready mentioned central senile areolar
choroi dal atro phy,(57) Otto Haab was the first
to report one year later in 1885 on “Senile
Makulaerkrankung”, senile ma cu lar disease
as a separate entity among the macular dis-
eases (MDs), starting in the RPE (Fig. 1b).(27, 65, Figure 7
66) No other articles by Haab have come to Disciform macular degeneration.(84)
light, explaining why he decided that senile Male, 79 years old.
MD was a separate entity. He concluded from Round center, over 2.5 diopter prominence.
anal yzing over 50 000 patient files that senile Johannes Oeller himself painted this,
MD was about as frequent as trauma tic MD like all images in his atlas, in oil on canvas.
and myo pic macular affection. Senile MD was
often bila teral and one should be wary of the time.(86). Disciform was later used to des cribe
outcome of a mature cataract operation when a retinal angioma.(74) The first image of disci-
the fellow eye had this MD.(66) It is striking form macular disease (dMD) was pro ba bly
that Haab explicitly stated that drusen, image number 6 in Hermann Pagenstech er’s
“quite innocent changes in old persons,” had atlas called “Chor oido-Retinitis in the region
nothing to do with senile MD (Fig. 1a).(27) of the macula lutea” (Fig.8, p.149).(59,75) One
should not confuse this idea of a disc under
An article in 1893 by Fuchs on cir ci – the macular area with the later introd u ced
na te re ti ni tis, a circle of white flecks around clinical expression of a disciform reaction,
———————– Page 11———————–
ease of the retinal center…may appear some –
what bleak or dull. Would this be the reason
that they changed the title of their mono-
graph from “Er kran kung” (disease) to
“Entar tung,” (degen er a tion) in order to at-
tract attention?(75) So what I always con sider –
ed to be a mono graph on end-stage AMD was
act ually a mono graph on dMD caused by dif-
ferent retinal disor ders, including a few cases
with late AMD! Junius and Kuhnt could not
help the fact that for many years their names
were coupl ed to AMD. This was partly be-
cause Ver hoeff,(1) and later Duke-El der,(76) ad –
ded to the original title of their mono graph
the word “se nile” or started a sub-chap ter
with: “Se nile disciform degeneration of the
macula (of Junius and Kuhnt).”(76)
Figure 8 The limited know ledge or inte rest in
According to Junius and Kuhnt (75) the first drawing of dis- AMD around 1965 may be ap pa r ent from
ciform macular disease as seen in the eye by low magnifi-
cation after removal of the anterior segment. Duke Elder’s System of Oph thal mology. It
It was called Choroido-retinitis in the region of the ma- covered AMD in seven pages in the chapter
cula lutea. “Between the papilla and macula lutea is a “Uveal mani fes tations of systemic dis eases,”
whitish tract which extends downwards, becoming whiter, under the sub-head “Vas cular scle rosis,”
and terminates in a sharp point.”
This atlas was published in English and German.(59) using the terms “Senile Macular Chorio –
retinal degen eration, Senile macular degen –
meaning any develop ment of a neo vas cular er ation of Haab, (Haab named it senile
membrane under the macula, whatever its macula disease!) or Senile Macular Degener-
cause. The break through in relation to “disc – ation.”(76) Drusen were dealt with in a few
i form” MD, how ever, was the clas sic mono – pages under the sub-category “Sec ondary
graph by Paul Ju nius and his predecessor degenerat ions.” (54)
Her mann Kuhnt.(75) They described exhaus-
tively 10 cases with an age range from 36 to Ageing macula disorder
76 years, having a disci form pro c ess inclu ding Terminology showed fewer variations after
five mono cu lar ones, each with a good fellow 1965. Oph thal mol ogists gradually became
eye. One case received a diagnosis “disease” aware that “senile” MD is not a diagnosis pa-
of the reti nal center, one “degen er ation” of tients are eager to hear, quite apart from its
this center, and eight cases received both. Ju- visual im plications. “Age-determined” as a
nius and Kuhnt concluded that circinate re- substitute for “sen ile” was first used in Ger-
tinitis and disciform disease of the retinal many(77)and later age-related ap peared in the
center belonged to one large cluster of dis- American litera ture.(78) In Table 3, one may
eases. Only ca se I had increasing drusen-like see a gradual change after 1965 from senile
spots along the inferior temporal venule and maculo pa thy and age-related MD to age-re-
the term druse or col loid bo dy, did not other- lated macular disease, ageing macula dis ease,
wise appear in any description of their cases. ageing macula dis order, the latest term being
The word “senile” appeared once in case II “Autoimmune macular disorder (79)” (all ab-
with “senile vessel diseases.” The causes sug- breviated as AMD).
gested for the dis ciform disorders varied from
alco ho lism and lues to hyper tension and On the eve that an article of mine (80)
athero scle rosis. This monograph is valuable was due to go to the printer, I receiv ed a
for the follow ing three reasons: firstly, the ex- phone call from the editor-in-chief who wan –
cellent over view of the past literature on ted to change its title from Aging Ma cu la Dis-
dMD; se cond ly, the detailed color draw ings; order into Age-related Macular Degeneration.
and, fin al ly, it informed the wider public We agreed to change the title but when plac-
about dMD.(75) In the epilogue on page 132 ing my arguments for Aging Macula Disorder
was written: The expres sion disciform dis- at the end of the article, some of their tenor
———————– Page 12———————–
was lost. In the interest of greater clarity, I Abbreviations
will summarize my arguments here:
AMD age-related macular degeneration
A good doctor should bur den the pa- age-related macular disease
tient with as little confusing or even alar m – ageing macula disease
ing infor ma tion as possible, especially when ageing macula disorder
it has no therapeutic conse quen ces. A few autoimmune macular disease
tiny drusen are not the same as late AMD. BrM Bruch’s membrane
The Ma cu lar Dis ease Society in the UK, re- dMD disciform macular degeneration
cently even dropped “Dis ease” from its name, disciform macular disorder
to the accompan iment of a huge round of ap- MD macular degeneration
plause by its members when this was an – macular disease
noun c ed at the annual mee t ing. macular disorder
RPE retinal pigment epithelium
We know many types of MD, often in
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