On the Current Care Situation and Treatment of Ocular Mucous Membrane Pemphigoid in Germany. / Zur Versorgungssituation und konservativen Therapie des okulären vernarbenden Schleimhautpemphigoids in Deutschland.

BACKGROUND: Ocular involvement in mucous membrane pemphigoid (MMP) is relatively rare, with a prevalence of 25 cases per million population, equating to approx. 2,100 patients throughout Germany. Diagnosis can be difficult - especially in cases of isolated ocular involvement - and treatment can be complex and lengthy. Immunosuppressants or immunomodulatory drugs are often used. Due to the complexity of diagnosis and treatment, MMP patients are usually referred to specialized centers. The aim of this project was to evaluate the current care situation of patients with ocular MMP in Germany. METHODS: A paper-based survey was designed and sent to all university eye clinics and other specialized centers in Germany in April 2020. The survey asked about the existence of a specialized outpatient service, the total annual number of patients with MMP, the annual number of newly diagnosed patients, any interdisciplinary collaboration for diagnostic or therapeutic purposes, as well as the local and systemic therapy used. RESULTS: Of a total of 44 clinics, 28 (64%) responded, reporting a total average of 27 ± 42 (0 - 200) patients and 3.6 ± 2.2 (0 - 10) new cases per year. This corresponds to a total of 741 patients. Only nine (32%) of the responding clinics offer specialized MMP clinics. 93% of the centers collaborate with the local dermatology department. 79% perform serological and histological diagnostics in-house. About half of the centers (n = 16) apply a standardized treatment regime. Systemic glucocorticoids (66.7%) are most commonly used, followed by mycophenolate mofetil and dapsone (57.1%), rituximab (33.3%), azathioprine and cyclophosphamide (28.6%), as well as methotrexate (19.0%). The least frequently used treatment is intravenous immunoglobulin (14.3%). CONCLUSION: This survey of German ophthalmology departments obtained data from about one third of the estimated total cohort of all patients with MMP in Germany. These are presumed to be exclusively patients with at least one ocular involvement. The complex care of these patients is usually provided in collaboration with a dermatologist and with the use of systemic anti-inflammatory medication. Currently, an ophthalmological MMP register is being established to better record the epidemiology and care situation of this rare disease in Germany and to improve it in the long term.

Clinicopathological Correlation of Microbial Keratitis and Ahead: Is There a Corneal Sepsis? / Zur klinisch-pathologischen Korrelation der mikrobiellen Keratitis und darüber hinaus: Gibt es eine korneale Sepsis?

Microbial, infectious keratitis is a relevant indication for penetrating keratoplasty. The requirement for transplantation results in histopathological examination of the entire thickness of the cornea. Although the clinical diagnosis is not always possible to confirm, pathology can support diagnostic evidence of clinical presentation and pathogenesis. This is achieved with multiple methods from cytology, histochemistry, immunohistology, molecular pathology and in rare cases electron microscopy. These allow tissue-based detection of previous and parallel diseases and the responsible pathogens. The failure of satisfactory clinicopathological correlation raises the question whether a suspected pathogen was not ultimately responsible for destroyed corneal tissue. The pathogenesis of keratitis requiring transplantation is not yet completely understood, also on the experimental level. The development of such a keratitis can lead to a clinical symptomatology which can be described as "threatening organ dysfunction", a term used in sepsis research. Considering recent literature, possible correlations between sepsis and microbial keratitis and their relation to histopathology are discussed.

Long-term results of glaucoma drainage device surgery.

BACKGROUND: To evaluate long-term results of eyes with glaucoma drainage device (GDD). METHODS: We retrospectively reviewed medical records of all patients who underwent GDD placement at our institution between 2001 and 2014. A total of 110 eyes of 90 patients were studied. Glaucoma outcome was assessed by postoperative intraocular pressure (IOP), number of medications, and need for further glaucoma surgery. Surgical procedures before and during the study period, and their complications were evaluated. RESULTS: The mean follow-up was 78.3 ± 44.0 months. The mean preoperative intraocular pressure was 30.8 ± 6.9 mmHg with 3.5 ± 1.1 glaucoma medications. At last postoperative follow-up, the mean IOP decreased to 14.3 ± 5.4 mmHg with 1.6 ± 1.5 glaucoma medications. GDD implantation successfully controlled glaucoma in 86, 85, 81, 78, 79, 76 and 73% of eyes at 1, 2, 3, 4, 5, 7 and 10 years, respectively. At last follow-up IOP was successfully controlled in 67% of eyes. Clinical complications occurred in 56.4% of eyes during the follow-up period. CONCLUSIONS: A glaucoma drainage device can successfully control intractable glaucoma even after a very long period of time.

Open globe and penetrating eyelid injuries from fish hooks.

BACKGROUND: A few case reports have described accidental eye injuries caused by fish hooks. The severity of ocular injuries is dependent on the involved ocular structures. Severe ocular injuries due to fish hooks are rare. We describe open globe and penetrating eyelid injuries from fish hooks at the Baltic Sea. METHODS: Nine patients with traumatic ocular injuries caused by fish hooks were included. The following parameters were evaluated: severity of injury, best corrected visual acuity at admission and last follow-up, and surgical treatment. RESULTS: All nine patients were male. Age ranged between 7 and 51 years with a median of 13 years. Sixty-seven percent of the patients were children. Four of the nine patients were 9 years or younger. In 5 eyes (55%) the injury was limited to the eyelid. An open globe injury was found in 4 patients (45%). The mean follow-up was 16.7 ± 32.8 months. All patients required surgical treatment. The number of operations ranged from 1 to 3, with a mean of 1.4. At admission and last follow-up, patients with eyelid injuries showed a median best corrected visual acuity (BCVA) of logMAR 0.0. Patients with open globe injuries showed a median best corrected visual acuity of logMAR 1.5 at admission, and of logMAR 0.6 at last follow-up. CONCLUSIONS: Nearly half of the patients suffered severe penetrating injuries. Especially children misjudge the risk potential of fishing due to their lack of experience. Fishing glasses should be worn not only for UV protection, but also as injury prevention strategy.

Variability of panretinal photocoagulation lesions across physicians and patients. Quantification of diameter and intensity variation.

BACKGROUND: Photocoagulation lesion intensity relies on the judgement of retinal blanching. Lesions turn out variable due to observer-dependent judgement and time dependency of blanching. We investigated lesion variability per patient and per physician in clinical routine treatments. METHODS: In this observational clinical trial, different physicians performed panretinal photocoagulation for diabetic retinopathy. Study eyes received 20-30 study lesions at 20 ms (three physicians, nine eyes) and 200 ms (four physicians, 12 eyes) irradiation time (532 nm continuous wave photocoagulator, 300 µm spot size). Lesions were imaged after 1 hour with photography and optical coherence tomography (OCT). We measured lesion diameters in fundus and OCT images, and graded intensities according to a previously published six-step classifier. RESULTS: 200-ms lesions were larger and more severe (568, 474-625 µm [median, IQR], predominantly class 6) than 20-ms lesions (397, 347-459 µm, predominantly classes 3-4). The impact of laser power was small compared to other factors. Lesion intensities and diameters in fundus and OCT images varied significantly between patients and between physicians. Median photographic lesion diameters varied by up to a factor of 1.61 (20 ms) or 1.5 (200 ms) respectively. CONCLUSIONS: In this study, the treated area of retina varied by up to a factor of 1.612 = 2.59 for a given spot number. As clinical efficacy depends on the treated area, which is a function of lesion number by area per lesion, our results implicate poor control of the overall treatment effect if treatments are administered according to lesion number or spacing alone. Better ways of laser effect control should be sought.

Photocoagulation in rabbits: optical coherence tomographic lesion classification, wound healing reaction, and retinal temperatures.

BACKGROUND AND OBJECTIVE: The rabbit is the most common animal model to study retinal photocoagulation lesions. We present a classification of retinal lesions from rabbits, that is based on optical coherence tomographic (OCT) findings, temperature data, and OCT-follow-up data over 3 months. MATERIALS AND METHODS: Four hundred eighty-six photocoagulation lesions (modified Zeiss Visulas® 532 nm CW laser, lesion diameter 133 µm, exposure duration 200 milliseconds or variable, power variable) were analyzed from six eyes of three chinchilla gray rabbits. During the irradiation of each lesion, we used an optoacoustics-based method to measure the retinal temperature profile. Two hours, 1 week, 1 month, and 3 months after the treatment, we obtained fundus color and OCT (Spectralis®) images of each lesion. We classified the lesions according to their OCT morphology and correlated the findings to ophthalmoscopic and OCT lesion diameters, and temperatures. RESULTS: Besides an undetectable lesion class 0, we discerned subthreshold lesions that were invisible on the fundus but detectable in OCT (classes 1 and 2), very mild lesions that were partly visible on the fundus (class 3), and 3 classes of suprathreshold lesions. OCT greatest linear diameters (GLDs) were larger than ophthalmoscopic lesion diameters, both increased for increasing classes, and GLDs decreased over 3 months within each class. Mean peak end temperatures for 200 milliseconds lesions ranged from 61°C in class 2 to 80°C in class 6. CONCLUSION: The seven step rabbit lesion classifier is distinct from a previously published human lesion classifier. Threshold lesions are generated at comparable temperatures in rabbits and humans, while more intense lesions are created at lower temperatures in rabbits. The OCT lesion classifier could replace routine histology in some studies, and the presented data may be used to estimate lesion end temperatures from OCT images.

Ten-Year Outcome of Glaucoma Drainage Device Surgery After Penetrating Keratoplasty.

PRECIS: In eyes with intractable glaucoma, drainage devices provide long-term control of intraocular pressure also after penetrating keratoplasty (PK). There is a high incidence of corneal graft failure. PURPOSE: To compare very long-term results of eyes with glaucoma drainage device (GDD) after PK. METHODS: We retrospectively reviewed medical records of all patients who underwent GDD placement after PK at our institution between 2001 and 2017. Forty eyes of 40 patients were studied. Glaucoma outcome was assessed by postoperative intraocular pressure (IOP), number of medications, and need for further glaucoma surgery. Corneal outcome was assessed by graft rejection, failure, and visual acuity. Surgical procedures before and during the study period, and their complications were evaluated. RESULTS: The mean follow-up was 125.0±52.3 (median, 116.5) months. Twenty of 40 eyes had a follow-up of at least 10 years. The mean preoperative IOP was 34.0±8.3 (median, 32.0) mm Hg with 3.2±1.3 (median, 3.5) glaucoma medications. At last postoperative follow-up, the mean IOP decreased to 12.7±4.9 (median, 14.0) mm Hg with 1.0±1.2 (median, 0.0) glaucoma medications. GDD implantation successfully controlled glaucoma in 88%, 88%, 85%, 80%, 78%, 75%, and 70% of eyes, at 1, 2, 3, 4, 5, 7, and 10 years, respectively. At last follow-up 68% showed glaucoma success. The corneal grafts remained clear in 74%, 63%, 45%, 45%, 37%, 32%, and 26% of eyes at 1, 2, 3, 4, 5, 7, and 10 years, respectively. Only 7 corneal grafts (17.5%) remained clear at last follow-up. CONCLUSIONS: A GDD can successfully control intractable glaucoma even after a very long period of time also after PK. However, the survival of the corneal grafts is low.

Implantation of retropupillar iris claw lenses with and without combined penetrating keratoplasty.

BACKGROUND: For aphakic patients without lens-supporting apparatus, secondary lens implantation can be considered. Literature on retropupillar iris claw lens implantation as a safe alternative to scleral fixated posterior chamber lenses is scarce. METHODS: The study included 22 patients. In ten cases, an iris claw lens was implanted retropupillary without penetrating keratoplasty (group 1), in 12 patients the implantation of a retropupillar iris claw lens was combined with penetrating keratoplasty (group 2). Complications observed were retrospectively evaluated. Previous operations and accompanying diseases were compiled. Reasons for aphakia in group 1/group 2 included perioperative complications (60%/75%) and primary ocular trauma (40%/25%). Unless already performed in an earlier operation, anterior or complete vitrectomy was performed in both groups. RESULTS: Perioperative complications (within 1 week postoperatively) in group 1 included ocular hypotony in 20%, choroidal detachment in 10%, vitreous haemorrhage in 10% and intraocular lens (IOL) decentration in 10% of the cases; in group 2, transient intraocular pressure elevation in 8% of the cases. Postoperative complications (after the first postoperative week) in group 1 were lens tilt in 10%, lens luxation in 10%, cellular deposits (assumed to be macrophages) on lens surface in 10%, cornea guttata in 10% and epiretinal gliosis in 10% of the cases; in group 2, secondary glaucoma in 33%, iris defect in 8% and corneal ulcer in 8% of the cases. CONCLUSIONS: Retropupillar iris claw lenses are an alternative to scleral fixated secondary lenses, which are worth considering for aphakic patients without lens supporting apparatus. This approach appears to be recommendable even in cases requiring penetrating keratoplasty, and can be performed as a combined procedure. In these patients, the most frequent complication following iris claw lens implantation seems to be secondary glaucoma.

Comprehensive detection, grading, and growth behavior evaluation of subthreshold and low intensity photocoagulation lesions by optical coherence tomographic and infrared image analysis.

PURPOSE: To correlate the long-term clinical effect of photocoagulation lesions after 6 months, as measured by their retinal damage size, to exposure parameters. We used optical coherence tomographic (OCT)-based lesion classes in order to detect and assess clinically invisible and mild lesions. METHODS: In this prospective study, 488 photocoagulation lesions were imaged in 20 patients. We varied irradiation diameters (100/300 µm), exposure-times (20-200 ms), and power. Intensities were classified in OCT images after one hour, and we evaluated OCT and infrared (IR) images over six months after exposure. RESULTS: For six consecutive OCT-based lesion classes, the following parameters increased with the class: ophthalmoscopic, OCT and IR visibility rate, fundus and OCT diameter, and IR area, but not irradiation power. OCT diameters correlated with exposure-time, irradiation diameter, and OCT class. OCT classes discriminated the largest bandwidth of OCT diameters. CONCLUSION: OCT classes represent objective and valid endpoints of photocoagulation intensity even for "subthreshold" intensities. They are suitable to calculate the treated retinal area. As the area is critical for treatment efficacy, OCT classes are useful to define treatment intensity, calculate necessary lesion numbers, and universally categorize lesions in clinical studies.

Correlation with OCT and histology of photocoagulation lesions in patients and rabbits.

PURPOSE: To examine spectral domain optical coherence tomographic (OCT) and histological images from comparable retinal photocoagulation lesions in rabbits, and to correlate these images with comparable OCT images from patients. METHODS: 508 rabbit lesions were examined by HE-stained paraffin histology. 1019 rabbit lesions versus 236 patient lesions were examined by OCT, all at the time-points 1 hr, 1 week and 4 weeks after photocoagulation. We analysed 100 µm lesions (in humans) and 133 µm lesions (in rabbits) of 200 ms exposures at powers titrated from the histological threshold up to intense damage. Lesions were matched according to morphological criteria. RESULTS: Dome-shaped layer alterations, retinal infiltration by round, pigmented cells, outer nuclear layer interruption, and eventually full thickness retinal coagulation are detectable in histology and OCT. Horizontal damage extensions are found 1½ times larger in OCT. More intense irradiation was necessary to induce comparable layer affection in rabbit OCT as in histology. Restoration of the inner retinal layers is only shown in the OCT images. Comparable primary lesions caused more pronounced OCT changes in patients than in rabbits during healing. CONCLUSIONS: Optical coherence tomographic images indicate different tissue changes than histologic images. After photocoagulation, they show wider horizontal damage diameters, but underestimate axial damage particularly during healing. Conclusions on retinal restoration should not be drawn from OCT findings alone. Retinal recovery after comparable initial lesions appears to be more complete in rabbit than in patient OCTs.

Correlation of temperature rise and optical coherence tomography characteristics in patient retinal photocoagulation.

We conducted a study to correlate the retinal temperature rise during photocoagulation to the afterward detected tissue effect in optical coherence tomography (OCT). 504 photocoagulation lesions were examined in 20 patients. The retinal temperature increase was determined in real-time during treatment based on thermoelastic tissue expansion which was probed by repetitively applied ns laser pulses. The tissue effect was examined on fundus images and OCT images of individualized lesions. We discerned seven characteristic morphological OCT lesion classes. Their validity was confirmed by increasing visibility and diameters. Mean peak temperatures at the end of irradiation ranged from approx. 60 °C to beyond 100 °C, depending on burn intensity.

Temperature-controlled retinal photocoagulation--a step toward automated laser treatment.

PURPOSE: Retinal laser photocoagulation carries the risk of overtreatment due to effect variation of identically applied lesions. The degree of coagulation depends on the induced temperature increase and on exposure time. We introduce temperature controlled photocoagulation (TCP), which uses optoacoustics to determine individually exposure times necessary to create reproducible lesions. METHODS: Optoacoustic temperature measurement relies on pressure waves that are excited in the retinal tissue by repetitive low-energy laser pulses. Signal amplitudes correlate with tissue temperature and are detected by a transducer in the laser contact lens. We used a continuous wave (CW) photocoagulator for treatment irradiation and superimposed probe laser pulses for simultaneous temperature measurement. Optoacoustic data of 1500 lesions (rabbit) were evaluated to develop an algorithm that controls exposure times automatically in TCP. Lesion diameters of 156 TCP lesions were compared to 156 non-controlled lesions. Histology was performed after 1 hour, and 1 and 4 weeks. RESULTS: TCP resulted in exposure times from 4 to 800 ms depending on laser power chosen. Ophthalmoscopic and histologic lesion diameters were independent of power between 14 and 200 mW. TCP lesions barely were visible with a mean diameter equal to the treatment beam (130 µm). In contrast, standard lesion diameters increased linearly and statistically significantly with power. Histology confirmed sparing of the ganglion and nerve fiber layers in TCP. CONCLUSIONS: TCP facilitates uniform retinal lesions over a wide power range. In a clinical setting, it should generate soft and reproducible lesions independently of local tissue variation and improve safety, particularly at short exposure times.