Goblet cells of the conjunctiva are the main source of mucus for the ocular surface. The objectives of this review are to consider the goblet cells as assessed by various histological, cytological and electron microscopy methods, and to assess the consistency of published reports (over more than 25 years) of goblet cell density (GCD) from impression cytology specimens from nominally healthy human subjects. Reported GCD values have been notably variable, with a range from 24 to 2226 cells/mm² for average values. Data analysis suggests that a high density of goblet cells should be expected for the healthy human conjunctiva, with a tendency toward higher values in samples taken from normally covered locations (inferior and superior bulbar conjunctiva) of the open eye (at 973 +/- 789 cells/ mm²) than in samples taken from exposed (interpalpebral) locations (at 427 +/- 376 cells/mm²). No obvious change in GCD was found with respect to age, perhaps because the variability of the data did not allow detection of any age-related decline in GCD. Analyses of published data from 33 other sources indicated a trend for GCD to be lower than normal across a spectrum of ocular surface diseases.

Goblet Cells of the Normal Human Bulbar Conjunctiva and Their Assessment by Impression Cytology Sampling

Impression cytology (IC) allows cells to be harvested from the ocular surface noninvasively. Superficial layers of the epithelium are removed by application of cellulose acetate filters or Biopore membranes, and the cells can be subsequently analyzed by various methods, depending on the objective of the investigation or pathology involved. IC techniques are easily learned, can be performed in an outpatient setting, and cause virtually no discomfort to the patient. IC facilitates the diagnosis of ocular surface disorders, including, among others, keratoconjunctivitis sicca, ocular surface squamous neoplasia, and ocular surface infections. During the past decade, IC has been used increasingly to assist in diagnosis of ocular surface disease, improve our understanding of the pathophysiology of ocular surface disease, and provide biomarkers to be used as outcome measures in clinical trials. Dry eye disease is one area in which IC has contributed to significant advances.

Impression Cytology: Recent Advances and Applications in Dry Eye Disease

Purpose To compare the loss of corneal endothelial cells after phacoemulsification according to different anterior chamber depths (ACDs) Methods We conducted a prospective study on 135 eyes with senile cataracts Eyes with nuclear density grades of 2 to 4 were divided into three groups according to ACD: ACD I, 15 005) Endothelial cell loss was significantly higher in ACD I than in ACD III in grades 3 and 4 cataract density groups 2 months after phacoemulsification (P < 005) There were also more changes in CCT in all of the cataract density groups in the ACD I group compared to the ACD II and III groups 2 months postoperatively, but the difference was not statistically significant Conclusions Eyes with shallow ACDs, especially those with relatively hard cataract densities, can be vulnerable to more corneal endothelial cell loss in phacoemulsification surgery

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Endothelial Cell Loss after Phacoemulsification according to Different Anterior Chamber Depths

Carotenoids are lipophilic isoprenoid pigments with a common C40H56 core chemical structure that are naturally synthesized by many plants, algae, bacteria, and fungi. Humans and animals cannot synthesize carotenoids de novo and must obtain them solely through dietary sources. Among the more than 750 carotenoids in nature, only lutein, zeaxanthin, meso-zeaxanthin, and their oxidative metabolites selectively accumulate in the foveal region of the retina where they are collectively referred to as the macular pigment (MP) of the macula lutea. MP serves an ocular protective role through its ability to filter phototoxic blue light radiation and also via its antioxidant activity. These properties have led to the hypothesis that carotenoids may protect against the development of age-related macular degeneration (AMD), the most common cause of blindness in the aged population >60 years old. Epidemiological studies have supported this by showing that patients with lower concentrations of serum carotenoids and macular pigment optical density (MPOD) measurements are at a higher risk of developing AMD. Conversely, nutritional supplementation and diets rich in lutein and zeaxanthin readily impact MP concentrations and reduce the risk of progression to advanced AMD, and the AREDS2 supplement formulation containing 10 mg of lutein and 2 mg of zeaxanthin is the standard-of-care recommendation for individuals at risk for visual loss from advanced AMD. This article reviews the rich history of research on the MP dating back to the 1700s and outlines their potential for further therapeutic improvements for AMD in the future.

What do we know about the macular pigment in AMD: the past, the present, and the future.

Purpose: To assess the relationship between postoperative endothelial cell loss and microcoaxial phaco parameters using Ozil IP (Alcon Laboratories, Inc, Fort Worth, TX) in noncomplicated cataract surgery. Methods: In this prospective observational study, 120 consecutive cases of cataract patients with different grades of nuclear hardness underwent microcoaxial phacoemulsification through a 2.2-mm clear corneal incision. An Alcon Infinity Vision System with Ozil IP (Alcon Laboratories) was used with an Ozil torsional handpiece and a Kelman-style 45° phacoemulsification tip. Patients underwent preoperative and postoperative central endothelial cell counts. Results: The study included 120 cases of age-related cataract whose mean age (standard deviation [SD]) was 59.68 years (9.47). There was a highly statistically significant endothelial cell loss (P , 0.001). The endothelial cell loss ranged 11–1149 cells/mm 2 with a median (interquartile range) of 386 cells/mm 2 (184.5–686 cells/mm 2 ). The percentage of postoperative ECLoss% ranged from 0.48% to 47.8% with a median (interquartile range) of 15.4% (7.2% to 26.8%). A significant positive correlation was found between the ECLoss% and different phaco parameters. The Spearman’s rank-order correlation coefficient values, rho, (ρ) were as follows: CDE (ρ = 0.425), aspiration time (ρ = 0.176), and volume (ρ = 0.278). Also, ECLoss% was significantly correlated with the grade of nuclear opalescence (Kendall’s tau τ = 0.42). Conclusion: Microcoaxial phacoemulsification was efficient in removing noncomplicated cataracts; however a statistically significant endothelial cell loss was noted, especially with increased nuclear hardness. This endothelial cell loss was mostly related to the increased cumulative dissipated energy (CDE), aspiration time, and volume of balanced salt solution used.

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Relationship between endothelial cell loss and microcoaxial phacoemulsification parameters in noncomplicated cataract surgery

Purpose To compare the intraoperative and postoperative outcomes of conventional longitudinal phacoemulsification and torsional phacoemulsification. Setting Department of Ophthalmology, University of Leipzig, Germany. Design Randomized single-center clinical trial. Methods Eyes with senile cataract were randomized to have phacoemulsification using the Infiniti Vision System and the torsional mode (OZil) or conventional longitudinal mode. Primary outcomes were corrected distance visual acuity (CDVA) and central endothelial cell density (ECD), calculated according to the Conference on Harmonisation-E9 Guidelines in which missing values were substituted by the median in each group (primary analysis) and the loss was then calculated using actual data (secondary analysis). Secondary outcomes were ultrasound (US) time, cumulative dissipated energy (CDE), and percentage total equivalent power in position 3. Postoperative follow-up was at 3 months. Results The mean preoperative CDVA was 0.41 logMAR in the torsional group and 0.38 logMAR in the longitudinal group, improving to 0.07 logMAR postoperatively in both groups. The mean ECD loss was 7.2% ± 4.6% in the torsional group (72 patients) and 7.1% ± 4.4% in the longitudinal group (76 patients), with no statistically significant differences in the primary analysis (P = .342) or secondary analysis (P = .906). The mean US time, CDE, and percentage total equivalent power in position 3 were statistically significantly lower in the torsional group (98 patients) than in the longitudinal group (94 patients) (P Conclusion The torsional mode was as safe as the longitudinal mode in phacoemulsification for age-related cataract. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Comparison of endothelial changes and power settings between torsional and longitudinal phacoemulsification

To document with spectral-domain optical coherence tomography the structural stabilization of the fovea and the sealing of outer macular defects by Muller cells.
 A retrospective case series of 45 eyes of 34 patients is described. In cases of a cystic disruption of the foveola as in macular telangiectasia type 2 and vitreomacular traction, the Muller cell cone provides the structural stability of the fovea. In cases of a detachment or disruption of the Muller cell cone, e.g., in foveal pseudocysts, outer lamellar holes, and degenerative and tractional lamellar holes, Muller cells of the foveal walls may provide the structural stability of the fovea by the formation of a hyperreflective external limiting membrane (ELM) which bridges the holes in the central outer nuclear layer (ONL). Muller cells of the foveal walls and parafovea mediate the regeneration of the foveal architecture in cases of outer lamellar and full-thickness macular holes. The regeneration proceeds by a centripetal displacement of photoreceptor cell somata which closes the holes in the central ONL. The closure may be supported by the formation of a glial tissue band at the ELM which seals the hole. The Muller cell cone provides the foveal stability in cases of a cystic disruption of the foveola. The structural stability of the outer foveal layers is mainly provided by the Muller cells of the foveal walls and parafovea; these cells also mediate the regeneration of the outer fovea in cases of a defect of the central ONL.

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Two different populations of Müller cells stabilize the structure of the fovea: an optical coherence tomography study

The pathogenesis of partial-thickness macular defects and the role of Muller glial cells in the development of such defects are not well understood. We document the morphological characteristics of various types of partial-thickness macular defects using spectral-domain optical coherence tomography, with the focus on tractional and degenerative lamellar holes, and discuss possible pathogenic mechanisms. A retrospective case series of 61 eyes of 61 patients with different types of partial-thickness macular defects is described. Partial-thickness macular defects are caused by anteroposterior or tangential traction onto the fovea exerted by the partially detached posterior hyaloid and epiretinal membranes, respectively. Tractional elevation of the inner Muller cell layer of the foveola—without (outer lamellar holes, foveal pseudocysts) or with a disruption of this layer (tractional lamellar holes, macular pseudoholes)—produces an elevation of the inner layers of the foveal walls (nerve fiber layer to outer plexiform layer [OPL]) and a schisis between the OPL and Henle fiber layer (HFL). With the exception of outer lamellar holes, the (outer part of the) central outer nuclear layer and the external limiting membrane remain nondisrupted in the various types of partial-thickness defects. Degenerative lamellar holes are characterized by cavitations between the inner plexiform layer and HFL of the foveal walls; many cases have lamellar hole-associated epiretinal proliferation (LHEP). Proliferating cells of the disrupted Muller cell cone may contribute to the development of LHEP and fill the spaces left by degenerated photoreceptors in the foveal center. It is suggested that morphological characteristics of partial-thickness macular defects can be explained by the disruption of the (stalk of the) Muller cell cone in the foveola and the location of tissue layer interfaces with low mechanical stability: the boundary with no cellular connections between both Muller cell populations in the foveola, and the interface between the OPL and HFL in the foveal walls and parafovea. We propose that the development of the cavitations in degenerative lamellar holes is initiated by traction which produces a schisis between the OPL and HFL, and enlarged by a slow and chronic degeneration of Henle fibers and bipolar cells. Trial registration retrospectively registered, #143/20-ek, 04/03/2020

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Morphology of partial-thickness macular defects: presumed roles of Müller cells and tissue layer interfaces of low mechanical stability.

To evaluate the influence of anterior chamber depth (ACD), anterior chamber volume (ACV), lens density (LD), and axial length (AL) as risk factors on endothelial cell loss 3 months after cataract surgery. We enrolled 47 patients with senile cataract who were operated between July 2012 and March 2013 by the same surgeon using torsional phacoemulsification. Preoperatively, we measured ACD, ACV, and LD using the Oculus Pentacam®. The AL was determined using the IOL Master®. Primary outcomes were central endothelial density (ECD) and corrected distance visual acuity (CDVA) 3 months after surgery We evaluated the effect of ACD, ACV, LD, and AL as possible risk factors of postoperative percentage endothelial cell loss (ECL). The median age was 72 years. The median CDVA before surgery was 0.5 improving to 1.0 postoperatively. The median ECL was 5.2 % (range 1.7 %–7.6 %). These results are comparable to our previous study (median ECL 6.9 % after 3 months) [Reuschel et al. (2010) J Cataract Refract Surg]. The median ACD in our study was 2.56 mm (range 2.26 mm–2.8 mm). Median ACV was 144 mm3 (range 121 mm3–158 mm3]. The median LD was 12.4 (range 11.4–13.7). Median AL was 23.1 mm (range 22.7 mm–23.9 mm). Our correlation analysis showed no significant correlation between ACD, ACV, LD, AL, and postoperative ECL. ACD, ACV, AL, and LD were not identified as risk factors of postoperative endothelial cell loss in our analysis.

Influence of anterior chamber depth, anterior chamber volume, axial length, and lens density on postoperative endothelial cell loss.

Aim To describe using spectral-domain optical coherence tomography the regeneration of the foveal morphology after pars plana (re)vitrectomy surgery and gas tamponade combined with injection of autologous platelet concentrate to treat full-thickness macular holes, and to describe different anatomical outcome. Methods A retrospective case series of 8 eyes of 8 patients was described. Results In all cases investigated, the platelet-assisted closure of macular holes was associated with a rapid resolution of cystic cavities in the foveal walls. In two patients, there was a regular regeneration of the foveal morphology after hole closure; the regenerated central fovea had a regular structure with a foveola and photoreceptors. In three other patients, there was an irregular regeneration of the fovea; a foveola was not formed, photoreceptor cells were absent from the foveal center, and the center was composed of Muller and retinal pigment epithelial (RPE) cells. The foveal regeneration after hole closure may proceed with or without a temporary detachment of the foveal center from the RPE, and with or without a direct contact between the central outer nuclear layer (ONL) and the RPE. Contacts between the ONL and RPE were observed only in patients with an irregular foveal regeneration after hole closure. Conclusion The data show that there are different modes of foveal regeneration after closure of macular holes with (re)vitrectomy and platelet concentrate. It is suggested that the regular regeneration of the foveal morphology proceeds by Muller cell-mediated tissue movements without cell proliferation, whereas the irregular foveal regeneration proceeds in part by proliferation of Muller and RPE cells.

Renate Wiedemann

Papers

Comparison of endothelial changes and power settings between torsional and longitudinal phacoemulsification

Two different populations of Müller cells stabilize the structure of the fovea: an optical coherence tomography study

Morphology of partial-thickness macular defects: presumed roles of Müller cells and tissue layer interfaces of low mechanical stability.

Influence of anterior chamber depth, anterior chamber volume, axial length, and lens density on postoperative endothelial cell loss.

Different modes of foveal regeneration after closure of full-thickness macular holes by (re)vitrectomy and autologous platelet concentrate