Impact of the COVID-19 pandemic's first wave on the care and treatment situation of intravitreal injections in a German metropolitan region.

PURPOSE: This study aims to evaluate the impact of the first coronavirus 2019 (COVID-19) wave in 2020 on patients scheduled for intravitreal injections (IVI) in a German metropolitan region. METHODS: We performed a multicentre prospective survey and retrospective analysis of the records of patients treated with intravitreal injections during the 20-week period from March to July 2020 in all four hospital eye departments in the city of Hamburg using a questionnaire (on treatment adherence, SarsCoV2-related personal, familial and social data) and treatment data. RESULTS: A total of 1038 patients (2472 IVI, 1231 eyes) and 818 questionnaires were evaluated. Longer duration of therapy, lower visual acuity (VA) of the treated and higher VA of the fellow untreated eye was were associated with a higher probability of visit cancellation. Every additional year of life posed a 2.6% lower risk of noncompliance. A COVID-19 infection in the family environment displayed a 5.5-fold chance of visit cancellation. Patients treated for neovascular age-related macular degeneration (nAMD) had a 36% reduced risk of visit cancellation compared to patients with diabetic macular oedema (DME). CONCLUSION: A long preceding treatment period, low VA of the treated eye, high VA of the untreated eye, COVID-19 in the family and DME were identified as risk factors for IVI visit cancellations during the COVID-19 pandemic. Compliance to treatment might be improved in the future by taking these risk factors into account when scheduling patients for IVI during the exceptional circumstances of a pandemic.

[Bilateral effusion syndrome induced by chlorthalidon]. / Chlortalidon als Ursache eines bilateralen Effusionssyndroms.

Uveal effusion can lead to anterior swelling of the choroid up to angle-closure glaucoma. This article reports the case of a 57-year-old male patient who presented with headache, vertigo and bilaterally reduced visual acuity. The examination showed a myopic shift and angle-closure glaucoma caused by uveal effusion. The medical history revealed that 3 days before the appearance of the symptoms, treatment with chlorthalidone was added to the antihypertensive medication. After discontinuation of the chlorthalidone intake the uveal effusion and its concomitant symptoms disappeared without residues.

[Tarsal Kink: Pathognomonic Presentation and Therapy of a Rare Congenital Upper Eyelid Malformation]. / Tarsusknickung ("Tarsal Kink"): Pathognomonische Präsentation und Therapie einer seltenen kongenitalen Oberlidfehlbildung.

BACKGROUND: Presentation of a congenital abnormality that is rare, but follows a distinct course and can be diagnosed and cured promptly if the pathognomonic presentation is recognized. A congenital tarsal kink leads to a malposition of the upper eyelid margin that must not be missed, as it will lead to ulcerative keratitis if it is not treated. CASE PRESENTATION: An otherwise healthy newborn was presented after delivery with forceps with marked unilateral purulent secretion and blepharospasm. DIFFERENTIAL DIAGNOSIS: Neonatal dacryocystitis, gonococcal infection, congenital entropion with ulcerative keratitis, tarsal kink. EXAMINATION: It was not possible to fully examine the lid and cornea with the baby awake. Due to total inversion of the lid margin, no lashes could be seen. Under general anesthesia, the tarsal kink, with complete inversion of the lid margin and a corneal ulcer, was confirmed. TREATMENT: The literature offers several methods to correct this rare malposition, all of which aim to strengthen the anterior lamella to correct the kink. After incision of the kink and repositioning of the tarsus and securing the position with fixation sutures, the ulcer healed quickly and completely; lid closure and lid contour were normal and symmetrical. SUMMARY: Complete inversion of the lid margin is the pathognomonic sign of tarsal kink, giving the impression of "missing" lashes, accompanied by blepharospasm, followed by purulent secretion and corneal ulceration. The condition must not be misdiagnosed as only immediate correction can prevent severe damage.

Expression profile of aquaporins in human nasolacrimal duct epithelium.

PURPOSE: To determine whether the epithelium of the human nasolacrimal ducts contains aquaporins (AQPs), a family of membrane proteins that function as selective pores and are able to transport water, glycerol, and other small solutes across the cell plasma membrane. METHODS: Expression of AQPs 0 and 1-10 in human nasolacrimal duct tissue was determined by reverse transcription polymerase chain reaction (RT-PCR). Positive PCR amplification products were verified by direct cDNA sequencing. Western blot analysis was used to detect AQPs 3-5. Antisera specific for AQPs were used in immunohistochemical analysis to determine the presence and distribution of ten AQPs (AQP 0 and 1-9) in epithelia and subepithelial glands of the nasolacrimal ducts. All samples investigated originated from human postmortem tissue. RESULTS: In human nasolacrimal duct samples, AQPs 1, 3, 4, 5, 7, 8, 9, and 10 were identified by RT-PCR. No RT-PCR products were detected for AQPs 0, 2, and 6. All AQPs, which were detected by RT-PCR, were also confirmed by direct sequencing of the cDNA. Immunohistochemical analyses revealed AQPs 1, 3, 5, 7, 8, and 9 in human nasolacrimal duct epithelium and were detected in different cells. Expression of AQP 4 could not be detected immunohistochemically but by Western blot analysis. Protein detection of AQP 10 could not be performed due to the unavailability of an appropriate antibody. CONCLUSIONS: The results suggest specific roles for AQPs in water transport through the epithelium of the nasolacrimal ducts and underline the presumption that tear fluid components are selectively absorbed in the nasolacrimal passage.

TFF peptides and mucins are major components of dacryoliths.

PURPOSE: The study was performed to determine whether trefoil factor peptides (TFF) and/or mucins are components of dacryoliths and to gain further insight into dacryolith composition and formation. METHODS: Twenty dacryoliths found in lacrimal surgery in patients suffering from primary acquired nasolacrimal duct obstruction were analyzed for the presence of TFF peptides (TFF1, 2, 3), mucins (MUC1, 2, 3, 4, 5AC, 5B, 6, 7, 8), defense cells (T- and B lymphocytes, macrophages, neutrophils), and antimicrobial substances (alpha defensins 1-3, secretory phospholipase A(2)) by means of light microscopy, histochemistry, immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR. RESULTS: All dacryoliths except one revealed clear immunoreactivity for all three TFF peptides. The immunohistochemical distribution of mucins was inhomogeneous throughout the different dacryoliths. However, in some dacryoliths all mucins investigated were detected. MUC8 showed reactivity in 14 out of 15 dacryoliths analyzed by immunohistochemistry. Most dacryoliths contained alpha defensins 1-3 as the secretory product of neutrophils. T and B lymphocytes, macrophages and secretory phospholipase A(2) were only present in single dacryoliths. Quantification of TFF peptide expression supported the immunohistochemical finding that all three TFF peptides are augmented in dacryoliths. CONCLUSIONS: Dacryoliths consist partly of secreted mucins comparable with the mucin spectrum of the epithelium of healthy nasolacrimal ducts. Beside TFF1 and TFF3, both of which are produced under healthy circumstances, TFF2 is additionally induced and secreted in cases of dacryolithiasis. All three TFF peptides appear to be augmented in dacryoliths. With regard to their rheologic properties, TFF peptides may play a functional role in dacryolith formation. However, our results raise the question of whether TFF peptides per se influence dacryolith formation or whether their secretion, as in secretion of mucins and alpha defensins 1-3, is merely a secondary phenomenon.

Differential expression of vascular endothelial growth factor implies the limbal origin of pterygia.

OBJECTIVE: To study the distribution of isoforms of vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 in pterygia and to compare it with that in healthy conjunctivas. DESIGN: Nonrandomized comparative (cadaver controlled) study with histopathologic correlations. METHODS: Tissue specimens from 75 patients treated for primary pterygia were analyzed using immunohistochemical studies as well as different molecular biological examinations. Healthy conjunctivas from 33 patients treated for cataracts as well as specimens from the conjunctiva, limbus, and lens of both eyes of 12 body donors served as controls. TESTING: Surgical specimens of pterygia and normal conjunctiva specimens were processed with paraffin, sectioned, stained using specific antibodies against VEGF and its receptors, and examined by light microscopy. The other part of both groups of specimens as well as specimens from body donors were prepared and analyzed by means of reverse-transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, enzyme-linked immunosorbent assay, and Western blots. MAIN OUTCOME PARAMETERS: Vascular endothelial growth factor and VEGFR1 and VEGFR2 were analyzed to indentify the splice variants of VEGF as well as the distribution and amount of VEGF and both receptors in pterygia and the control tissues. RESULTS: In analysis of specimens from pterygium patients as well as normal conjunctivas, VEGF121 and VEGF165 were identified as the only VEGF splice forms expressed. In addition to VEGF, VEGFR1 and VEGFR2 were detected in pterygia and conjunctivas and immunostained within the epithelium of pterygia and conjunctivas and on intrapterygial and intraconjunctival endothelial cells. Levels of VEGFR1 and VEGFR2 mRNA were lower in pterygia than in conjunctivas but similar in limbal and pterygium samples. Vascular endothelial growth factor levels were higher in pterygia than in conjunctivas, but were similar in the limbus and pterygia. CONCLUSIONS: The results reveal similar behaviors in limbal and pterygium epithelial cells in terms of VEGF and VEGFR expression, with the presumption that pterygia arise from limbal epithelial cells and that human conjunctivas are not a suitable control for the analysis of pterygia. Moreover, the results suggest that VEGF might play an active role in the physiology of conjunctival epithelial cells.

Upper and lower eyelid reconstruction for severe disfiguring necrobiotic xanthogranuloma.

BACKGROUND: Necrobiotic xanthogranuloma is a rare disease featuring generalized xanthomatous inflammatory skin lesions associated with paraproteinemia and possible lymphoproliferative diseases. Eyelid involvement can be unilateral or bilateral and ranges from minor xanthelasma-like lesions to severe ulcerative disease with consecutive keratitis and scleritis. CASE REPORT: The authors report the case of a 67-year-old woman with extensive necrobiotic xanthogranuloma involving the eyelids, head and neck, anterior chest, and both upper and lower extremities. Periorbital involvement caused severe upper and lower lid ectropium with chronic conjunctival inflammation and unilateral exposure keratitis. During a persistent period of low disease activity, granulomatous lesions and scars were widely excised, lids partially shortened and large full-thickness skin grafts applied. Uninvolved parts of the upper arms had to serve as donor sites, as other possible donor sites were not available. After successful reconstruction of the left side and no local recurrence of the disease, the right side was corrected in the same way. Full eyelid closure was achieved and skin grafts healed without complications. No recurrence of the disease appeared at the sites of operation, despite continuous new lesions elsewhere. CONCLUSION: Severe cicatricial eyelid deformation caused by necrobiotic xanthogranuloma can be treated with success by excision and free skin grafting. The mechanisms of recurrence at excision sites described by others remain unclear, but at least during phases of low activity, the described treatment is safe and recurrence is not to be expected.

Characterization of mucins in human lacrimal sac and nasolacrimal duct.

PURPOSE: Mucins are polymers that may reduce drag and enhance tear outflow. Mucin expression and distribution in human efferent tear ducts were tested in the physiological state, and potential differences in the expression pattern were investigated in the presence of primary acquired dacryostenosis (PANDO). METHODS: Expression of mucins in human lacrimal sac and nasolacrimal ducts was monitored by reverse transcription-polymerase chain reaction analysis. The presence and distribution of MUC1, -2, -4, -5AC, -5B, -6, and -7 in epithelia of the efferent tear duct passage are assessed with antisera to mucin peptide cores. Twenty normal tissues from cadavers and surgical specimens from 20 patients with PANDO were tested. RESULTS: mRNAs for all mucins investigated were detected in healthy human lacrimal sacs and nasolacrimal ducts. MUC6 mRNA was detected in only about half of the investigated samples. A reduced level of MUC2, -5AC, and -5B mRNAs was observed in PANDO. Immunohistochemistry revealed MUC2 in goblet cells and single epithelial cells. Both MUC5AC and -5B were detected in goblet cells forming intraepithelial mucous glands. MUC7 was present only in columnar epithelial cells of the efferent tear duct system. No immunoreactivity was observed with antibodies against MUC1, -4, and -6 peptide cores. CONCLUSIONS: Human efferent tear ducts express and produce a broad spectrum of mucins that is partly comparable with that in the conjunctiva and the salivary glands. The mucin diversity of the efferent tear ducts could enhance tear transport and antimicrobial defense. Reduced levels of mucin mRNA in a nonfunctioning though patent segment of the lacrimal passage, which is associated with epiphora, suggests that mucins ease tear flow through the efferent tear ducts.

Loss of tear duct-associated lymphoid tissue in association with the scarring of symptomatic dacryostenosis.

OBJECTIVE: To determine whether organized mucosa-associated lymphoid tissue (MALT) is a normal component of the human efferent tear ducts or is acquired in reaction to chronic inflammation. DESIGN: Nonrandomized comparative (cadaver controlled) study with histopathologic correlations. MATERIALS: Tissue specimens from nasolacrimal ducts of 38 patients undergoing endonasal dacryocystorhinostomy in postinflammatory dacryostenosis with signs of chronic inflammation were analyzed using histologic examination and immunohistochemical studies. Only tissue specimens revealing proliferative sclerotic forms of chronic fibrosis were chosen for the study. Eighty specimens from the lacrimal systems of body donors served as controls. TESTING: Tissue specimens from each lacrimal system were prepared and processed with paraffin, sectioned, stained using different histologic methods with an array of specific antibodies, and examined by light microscopy. MAIN OUTCOME PARAMETERS: The distribution of intraepithelial and subepithelial defense cells was analyzed to identify plasma cells, secretory immunoglobulins, lymphocytes, dendritic cells, and organized mucosa-associated lymphoid tissue. RESULTS: The presence of secretory immunoglobulin A was demonstrated in subepithelial plasma cells and in the cytoplasm of apical epithelial cells in both chronically inflamed and healthy lacrimal systems. In more than one third of cases from body donors, but in only a few biopsy specimens from patients, organized lymphoid tissue was found with the cytomorphologic and immunophenotypical features of MALT. All other cases showed a diffuse infiltrate of defense cells within the lamina propria. CONCLUSIONS: The development of tear duct-associated lymphoid tissue (TALT) is a common feature that is often found in symptomatically normal nasolacrimal ducts. Because TALT seems to be lost associated with the scarring of symptomatic dacryostenosis, it is unlikely that the presence per se of TALT leads to scarring. Future studies are needed to explain the development of TALT.

Drainage of tears: impact on the ocular surface and lacrimal system.

The human efferent tear ducts are part of the lacrimal system. Because little knowledge exists concerning the physiology of the nasolacrimal system, and hence its patho- physiology, the nasolacrimal system has received almost no consideration as a possible factor in dry eye. The human nasolacrimal ducts consist of the upper and the lower lacrimal canaliculus, the lacrimal sac, and the nasolacrimal duct. As a draining and secretory system, the efferent tear ducts play a role in tear transport and nonspecific immune defense. Moreover, components of tear fluid are absorbed in the nasolacrimal passage and are transported into a surrounding vascular system. This system is similar to a cavernous body that is subject to autonomic control and regulates tear outflow. Tear duct-associated lymphoid tissue (TALT) is present in the efferent tear ducts, displaying the cytomorphological and immunophenotypic features of mucosa-associated lymphoid tissue (MALT). Under normal conditions, tear fluid components are constantly absorbed into the blood vessels of the surrounding cavernous body. These vessels are connected to the blood vessels of the outer eye and could act as a feedback signal for tear fluid production, which ceases if these tear components are not absorbed. In this way, dry eye could be initiated. Defective stimulation of TALT could result in abnormal immune deviation at the ocular surface, leading to an autoimmunological response that causes dry eye pathology.

TFF peptides in the human efferent tear ducts.

PURPOSE: To determine whether the lining epithelium of the human lacrimal sac and nasolacrimal duct synthesizes TFF peptides (formerly P-domain peptides, trefoil factors), a family of mucin-associated secretory peptides. METHODS: Expression of TFF peptides in human lacrimal sac and nasolacrimal ducts was monitored by reverse transcription-polymerase chain reaction and Western blot analysis. Antisera specific for TFF peptides were used in immunohistochemical analysis to determine the presence and distribution of all three TFF peptides in epithelia of the lacrimal passage. The samples investigated originated from tissue obtained during surgery (18 patients) and postmortem tissue (10 specimens). RESULTS: mRNA expression of TFF1 and TFF3, but not TFF2, was detected in human lacrimal sac and nasolacrimal duct. TFF1 was detected in only approximately 50% of the investigated probes, whereas TFF3 was present in all samples. Immunohistochemistry revealed TFF1 (if present) to be associated with goblet cells forming intraepithelial mucous glands. TFF3 occurred in epithelial cells of the lacrimal sac and the nasolacrimal duct as well as in the acinar cells of subepithelial serous glands, but appeared to be absent in goblet cells. CONCLUSIONS: The epithelium of the nasolacrimal ducts synthesizes TFF3 and in some cases also TFF1. In contrast to the human conjunctiva, in which TFF3 is detectable only in goblet cells, TFF3 of the lacrimal sac and nasolacrimal duct is produced in large amounts by epithelial cells as well as by serous glands, but not-or in small amounts only-by goblet cells. This is comparable with localization of TFF3 in the major salivary glands. Thus, TFF3 may have a special function in tear transport through the lacrimal passage comparable to its function on the ocular surface, because the peptide, together with TFF1, may contribute to the rheologic properties of the tear film. Moreover, the TFF peptides may also influence epithelial healing with their motogenic properties.