From post-war reconstruction to the twenty-first century - ophthalmic pathology in Freiburg 1945-2015: review of 39,256 surgical specimens from various topographical regions collected over 71 years at a large German tertiary eye care centre

Abstract

Background: Ophthalmic pathology at the Eye Center at Medical Center, University of Freiburg, Germany, looks back on a tradition of more than 150 years. Surgical specimens and associated histological diagnoses have been archived since 1945. This study is the first of its size to include 39,256 specimens examined in a single ophthalmic pathology laboratory over 71 years.

Methods: We retrospectively studied ophthalmic pathology reports and clinical records of histological specimens archived between 1945 and 2015 and compared our results with 22 studies from the literature. Samples were grouped by localisation and histopathological diagnoses assigned to various categories. Both were coded and entered into a database together with the year of surgery, patient sex and age at excision.

Results: The patients' age at surgery was documented in 38,845 cases (99%), of which 19,601 were female (50.5%) and 19,244 were male patients (49.5%). The bimodal frequency distribution of specimens by patient age has a similar shape to that recorded 1941-1995 for Atlanta, USA and 1959-2021 for the Swedish population. Most specimens originated from the eyelid (50%), followed by cornea (16%), conjunctiva (14%), eyeball (9.1%), temporal artery (3.9%) and other locations (6.7%) comprising 16 less frequent topographies. The proportion of eyelid (corneal, conjunctival) lesions significantly increased fourfold (fivefold, twofold) during our study period (each p < .001); that of enucleations and temporal artery biopsies decreased significantly 38- and 3.6-fold (each p < .001). Concurrently, the numbers of eyelid, corneal, conjunctival and temporal artery specimens have significantly grown (each p < .001). Annual sample numbers increased significantly across the various medical directors' tenures (1945-1967: median = 78; 1968-1987: median = 454; 1988-2002: median = 670; 2003-2015: median = 1,445) (p < .001).

Conclusions: Historical events, general population developments and new surgical techniques and treatment options caused changes in the occurrence of various ocular and periocular specimens. Our study data contribute to providing an overall picture of the nature and relative frequency of ocular conditions leading to surgical excision of specimens with subsequent histopathological examination. A continuous sharp increase in case numbers since 1987 clearly exceeds the demographic trend emphasising the ever-growing importance of the sub-speciality of ophthalmic pathology. Ideally, histopathological assessments should be conducted by experienced ophthalmologists with surgical and pathology expertise, or by experienced pathologists with ophthalmology expertise, to ensure optimal patient care.

Keywords: Conjunctiva; Cornea; Eyeball; Eyelid; Ophthalmic pathology; Temporal artery; Time trends.

Fig. 1

Clinicopathological correlation from 1912. Hand-made illustration from our archive, drawn by Berta Axenfeld, Theodor Axenfeld’s wife, showing the clinical (A) and histological (B) appearance of an untreated conjunctivitis vernalis (spring catarrh) of 1 May 1912, labelled with handwritten notes by Theodor Axenfeld and bearing his signature (C). Axenfeld’s notes translate as follows: “Axenfeld. Freiburg/Br.” (above), “Spring catarrh. Conjunctiva of the upper fornix. Pronounced sclerotic stromal proliferation under the epithelium. Epithelial depressions. (Staining according to van Gieson)“ (bottom)

Fig. 2

Ophthalmopathological specimens examined 1945–2015. Changes in the number of specimens (n = 39,256) from main topographical regions examined during the study period (1945–2015); included are specimens submitted from external medical institutions and practising ophthalmologists since the mid-1990s. Other location: see Fig. 8. Duration of the respective medical directorship (→): Wegner 1945–1967, Mackensen 1968–1987, Witschel 1988–2002, Reinhard 2003–2015; commissioning of the new Freiburg Eye Center in 1964 (*); demographical development in Freiburg city (--): number of inhabitants; no data available 1948–49

Fig. 3

Ophthalmopathological specimens examined annually during four medical directorships. Box-whisker plots of the numbers of specimens examined each year, categorised into four groups according to the respective medical director’s tenure: 1945–1967 (Wegner; total: n = 1840), 1968–1987 (Mackensen; total: n = 7999), 1988–2002 (Witschel; total: n = 10,468) and 2003–2015 (Reinhard; total: n = 18,949). Minimum, first quartile [Q1], median (shown), third quartile [Q3], maximum and mean (x) of the annual number of specimens are for 1945–1967: 42, 60, 78, 98, 115 and 80; for 1968–1987: 154, 290, 454, 518.25, 556 and 400; for 1988–2002: 502, 615.5, 670, 766.5, 807 and 674.1; and for 2003–2015: 1005, 1154, 1445, 1704.5, 2046 and 1457.6. The annual number of specimens differed significantly across the various groups (p <.001)

Fig. 4

Ophthalmopathological specimens from external submitters 1994–2015. Changes in the number of specimens from main topographical regions submitted from external medical institutions and practising ophthalmologists (1994–2015). Other location: see Fig. 8

Fig. 5

Number of specimens by patient age. Frequency of specimens by age of all patients (n = 38,855; range: 0–108 years; median: 61 years), of female (n = 19,607; range: 0–108 years; median: 63 years) and of male patients (n = 19,248; range: 0–108 years; median: 58 years) at diagnosis during the study period (1945–2015). The three left-skewed distributions (all, f, m) each are non-normal (Shapiro–Wilk test: p <.001) and bimodal (Hartigans’ dip test: p <.001), with major modes at 72 (all), 74 (f) and 72 years (m) and minor modes at 1 year (all), 2 years (f) and 1 year (m)

Fig. 6

Topographical regions by patient age at surgery. Relative frequency of main topographical areas by patient age at surgery during the study period (1945–2015). Other location: see Fig. 8

Fig. 7

Changes in the relative frequency of specimens from main topographical regions. Relative frequency of samples from the main topographical areas received for histological examination within the 7 intervals of the study period (1945–2015). Other location: see Fig. 8. See text for statistical comparisons between the intervals

Fig. 8

Relative frequency of specimens from different topographical regions. Relative frequency of surgical specimens from various topographical areas received during the study period (1945–2015). The %-values given for the individual components of “other location” refer to the total of all localisations

Fig. 9

Changes in the number of samples and leading diagnostic categories from main topographical regions. Number of surgical specimens and associated leading histological diagnostic categories from main topographical areas within the 7 intervals of the study period (1945–2015). Other location: see Fig. 8