Corneal Microstructural Changes Research Articles

Comprehensive assessment of corneal microstructural changes following V4c implantable collamer lens surgery using in vivo confocal microscopy

BackgroundImplantable Collamer Lense (ICL) presents a viable alternative to conventional refractive surgeries, but their impact on corneal microstructure remains unclear. By employing in vivo confocal microscopy (IVCM), we examined changes in stromal and endothelial cells following the insertion of V4c ICLs, with the goal of enhancing post-surgical care and outcomes.MethodsIn this longitudinal investigation, we conducted detailed preoperative assessments on 103 eyes from 53 participants. Follow-up evaluations were carried out after surgery at set intervals: one day, one week, one month, three months, six months, and twelve months. We used IVCM to analyze changes in stromal and endothelial cells. To assess differences between pre- and post-surgery variables and to investigate correlations with age, axial length (AL), and spherical equivalent refraction (SER), we applied a repeated measures mixed-effects model, with statistical significance set at P < 0.05.ResultsNo vision-threatening complications were reported post-surgery. Significant reductions in stromal cell density (SCD) were observed postoperatively, with anterior and mid- SCD reaching their lowest values at 3 months and posterior SCD at 1 month, remaining below baseline at 12 months. endothelial cell density (ECD) and percentage of hexagonal cells (PHC) decreased initially, recovering by 12 months. Conversely, endothelial cellular area (ECA) and coefficient of variation of cell size (CoV) increased postoperatively, with the most significant change at 1 week. Endothelial deposits were detected in 49 of 101 eyes on postoperative day 1, half of them were absorbed within 3 months post-surgery. Changes in posterior SCD were negatively related to AL, while AL, SER, lens thickness showed associated with endothelium changes.ConclusionOur findings elucidate the corneal microstructural changes following V4c ICL implantation, particularly the significant early reductions in stromal and endothelial cell densities. We recommend careful management of viscoelastics during surgery to minimize endothelial deposits that may harm the endothelium. Enhanced early postoperative monitoring and these surgical adjustments can lead to improved surgical and post-surgical care, ultimately supporting better patient recovery.

Corneal microstructural changes of precise CHST6 gene mutation: a case series

BackgroundMacular corneal dystrophy (MCD) is an inherited, autosomal recessive disorder of defective keratan sulfate (KS) metabolism. It is caused by the mutations in carbohydrate sulfotransferase 6 gene (CHST6) which is essential for the sulfation of KS. Unlike the western world, MCD is the most common corneal stromal dystrophy in India, especially in south Indian population; it could be due to high frequency of consanguineous marriages.Case presentationThis study presents the clinical findings of one North Indian MCD family, including 6 patients and 3 unaffected relatives. We used slit lamp examination and in vivo confocal microscopy for assessment. Mutation screening was performed with Sanger sequencing, and corneal structure was analyzed through histochemistry and immunohistochemistry. Our comparative findings revealed that all the patients identified with the deletion of major portion of CHST6 that included the Open Reading Frame (ORF). Although all the patients showed significantly reduced central corneal thickness (CCT-250 μm), a drastic decrease in stromal keratocyte count, and depletion of Bowman’s layer compared to controls.ConclusionsThis study first time revealed that MCD patients from one family with a deletion of major portion of CHST6 that included ORF leads to severe corneal morphological changes.

Can unilateral lattice dystrophy be triggered by cataract surgery in an elderly patient?

ABSTRACT Purpose Aim is to report unilateral lattice corneal dystrophy (LCD) possibly triggered after cataract surgery in an elderly patient and to demonstrate anterior segment optic coherence tomography (AS-OCT) findings. Case Report A 77-year-old male presented with irritation and photophobia in the left eye. His medical history revealed that the patient had undergone cataract surgery on the left eye 5 months ago and his symptoms exaggerated after the surgery. Best corrected visual acuity (BCVA) was 20/32 in OD and 20/63 in OS. Slit lamp examination indicated clear cornea with nuclear sclerosis in the right eye, multiple fine lattice lines at the level of middle stroma in the left eye. The lattice lines extended radially but did not involve the limbus. The overlying epithelium was intact. AS-OCT was consistent with LCD in the left eye with the presence of hyperreflective material at the level of the middle stroma. In contrast, AS-OCT in the right eye showed a normal, healthy cornea. Conclusion LCD is an inherited disease that can rarely present with unilateral involvement. Apart from its unilaterality and lack of limbal-limbal extension, the time of onset of the lattice lines is another distinguishing feature of this case report. Herein, clinical findings appeared at an older age compared to the literature. In addition, the occurrence of findings after phacoemulsification surgery has raised the question that environmental factors may trigger the emergence of unilateral LCD in patients with genetic predisposition. It is not yet known whether unilateral LCD is an asymmetric and asynchronous presentation of bilateral LCD or a different entity triggered by external factors. AS-OCT enables to demonstrate the corneal microstructural changes, and confirm the diagnosis of unilateral LCD by showing that the fellow eye is healthy.

Dexpanthenol/sodium hyaluronate eye drops for corneal epithelial healing following corneal cross-linking in patients with keratoconus.

To evaluate the effect of dexpanthenol 2%/sodium hyaluronate 0.15% eye drops on corneal epithelial healing and corneal microstructural changes following corneal cross-linking (CXL) in patients with keratoconus. The study included 42 eyes of 21 patients with keratoconus who underwent CXL on both eyes. One eye of each patient was instilled dexpanthenol 2%/sodium hyaluronate 0.15% eye drops (DP/SH group) and the fellow eye was instilled unpreserved sodium hyaluronate 0.15% eye drops (SH group). The epithelial healing process was assessed every day until complete reepithelialization was achieved. The in vivo confocal microscopy (IVCM) findings were also recorded. The mean epithelial defect size 48.6 ± 6.7 mm2 for the DP/SH group and 48.2 ± 5.3 mm2 for the SH group. Complete reepithelialization was seen after 2.24 ± 0.44days (range 2-4days) in the DP/SH group and 3.43 ± 0.60days (3 to 5days) in the SH group. Posterior keratocyte density and endothelial cell density were similar in both groups. The mean subbasal nerve plexus density was significantly higher in the DP/SH group (postoperative 1month: 1.13 ± 1.51, 3months: 3.53 ± 2.55, 6months: 7.07 ± 1.42) compared to the SH group (postoperative 1month: 0.87 ± 1.43, 3months: 2.89 ± 2.62, 6months 6.33 ± 1.29). The DP/SH group revealed faster subbasal nerve regeneration and less edema compared to the SH group. Dexpanthenol 2%/sodium hyaluronate 0.15% eye drops were effective and safe for corneal epithelial healing, and promoted faster corneal reepithelialization, nerve regeneration, and keratocyte repopulation with reduced corneal edema compared to sodium hyaluronate eye drops.

Effects of lipid-containing eye drops on the ocular surface and in vivo confocal microscopy findings in patients using systemic isotretinoin

Objective To evaluate the effects of lipid-containing Rohto Dry Aid eye drops and sodium hyaluronate eye drops on the ocular surface and in vivo confocal microscopy (IVCM) findings in patients using systemic isotretinoin. Methods This retrospective study included 71 patients using systemic isotretinoin for acne vulgaris. Ocular surface and tear functions were evaluated with the tear break-up time (TBUT), corneal fluorescein staining (CFS), and the ocular surface disease index questionnaire (OSDI). Meibography was used for the staging of Meibomian gland dysfunction (MGD) while IVCM was used for the analysis of corneal micro-structural changes. The data of 36 patients using Rohto Dry Aid (the Rohto group) and 35 patients using sodium hyaluronate (the SH group) were recorded. Pre-treatment, first month and third month data were analyzed. Results Longer TBUT, lower OSDI score, and less CFS were observed in the first and third months after treatment in the Rohto group (p < 0.001). There was no significant change in TBUT and CFS in the first month (p > 0.05) in the SH group (p < 0.05) but lower TBUT and more CFS were observed in the third month. There was no significant change in the OSDI score in the SH group. There was a significant decrease in dendritic cells, activated keratocytes, and nerve tortuosity with IVCM in both groups. However, no significant difference was found between the two groups. Conclusion Rohto Dry Aid, with its support of the lipid layer, is an effective and safe treatment agent that can improve both ocular surface and IVCM findings in evaporative dry eye cases with MGD.

Retinal and Corneal Changes Associated with Intraocular Silicone Oil Tamponade.

Silicone oils (SO) are used as long-term intraocular tamponades and have an irreplaceable role in vitreoretinal surgery. They can, however, be associated with multiple and potentially severe complications, involving different ocular tissues, in particular retina and cornea. Recent advances in ophthalmic imaging have allowed the precise characterization of retinal and corneal microstructural changes, at a subclinical level. This detailed analysis of SO-related retinal and corneal changes has improved our understanding of their pathogenesis and offer the potential for optimized monitoring and management of patients with SO-filled eyes. This review aims to provide clinicians and ophthalmic scientists with an updated and comprehensive overview of the corneal and retinal changes associated with SO tamponade.

In vivo Imaging of Reis-Bücklers and Thiel-Behnke Corneal Dystrophies Using Anterior Segment Optical Coherence Tomography.

PurposeTo investigate in vivo corneal changes of genetically confirmed Reis–Bücklers corneal dystrophy (RBCD) and Thiel–Behnke corneal dystrophy (TBCD) using anterior segment optical coherence tomography (AS-OCT).DesignA single-center, prospective, comparative case series.MethodsSeven patients from 3 pedigrees (3 males, 4 females) with RBCD [Arg124Leu (R124L) heterozygous missense mutation of human transforming growth factor beta-induced (TGFBI) gene] and 4 patients from 3 pedigrees (3 males, 1 female) with TBCD [Arg555Gln (R555Q) heterozygous missense mutation of TGFBI gene] were examined. Six patients with RBCD and three patients with TBCD exhibited recurrence after corneal surgery including penetrating keratoplasty, phototherapeutic keratectomy, and electrolysis. All patients were examined by slit-lamp biomicroscopy followed by AS-OCT. Selected AS-OCT images of the cornea were evaluated qualitatively for changes in shape and degree of light reflection of corneal deposits.ResultsSlit-lamp biomicroscopy showed characteristic irregular gray opacities in Bowman’s layer in each dystrophy: a geographic pattern in RBCD and a honeycomb pattern in TBCD. In each dystrophy, distinct characteristic deposits were observed by AS-OCT as a banding lesion in Bowman’s layer and its adjacent epithelium/stroma. In RBCD, the banding lesion was highly reflective and sharply margined at the stroma. In contrast, deposits in TBCD in the same layer showed a saw-tooth pattern toward the epithelium and poorly margined at the stroma.ConclusionAS-OCT is able to clearly identify characteristic in vivo corneal microstructural changes associated with RBCD and TBCD. As a result, in vivo differentiation of RBCD and TBCD can be achieved.

Corneal Microstructural Changes by Confocal Microscopy in Vernal Keratoconjunctivitis Patients Treated with Topical Cyclosporine

ABSTRACT Purpose: To compare corneal morphologic changes in vernal keratoconjunctivitis (VKC) patients before and after treatment with topical cyclosporin (CsA). Methods: 23 VKC patients and 40 healthy subjects as controls were considered. All patients were treated with 1%CsA during their active phase. The impact of treatment on quality of life was evaluated administering the QUICK questionnaire. Both eyes were evaluated using the in vivo confocal microscopy (IVCM) before treatment (T0), at the end of treatment in Autumn (T1) and at the recurrence of symptoms in the next season (T2). Results: All VKC patients improved their QUICK scores after CsA treatment. IVCM highlighted corneal microstructural changes at the level of epithelium, sub-basal nerve plexus and stroma in patients affected by VKC and allowed to follow their evolution after topical treatment with CsA. Conclusions: IVCM is a valuable tool to evaluate the dynamic corneal changes in VKC before and after treatment with CsA.

Cornea verticillata in Fabry disease: a comparative study between slit-lamp examination and in vivo corneal confocal microscopy

PurposeTo compare the diagnostic power of slit-lamp examination with the in vivo corneal confocal microscopy (IVCM) as the gold standard in assessing the presence of corneal epithelial deposits in patients...

Early central and peripheral corneal microstructural changes in type 2 diabetes mellitus patients identified using in vivo confocal microscopy: A case-control study.

The aim of this study was to find early central and peripheral corneal microstructural changes in healthy subjects and type 2 diabetes mellitus (T2DM) patients with/without cornea fluorescein dot staining.This is a prospective case-control study of T2DM patients with/without cornea fluorescein dot staining. Age, sex, duration of diabetes, and serum glycosylated hemoglobin A1c (HbA1c) levels were recorded. Keratograph 5 M (K5 M) and in vivo confocal microscopy were performed on all subjects. The cornea was divided into 5 zones: central, superior, temporal, nasal, and inferior. Basal epithelial cell (BEC) density, the area of BEC, sub-basal nerve plexus (SBN) density, Langerhans cell (LC), and endothelial cell (EC) density were quantitatively analyzed.This study included a total of 87 individuals (28 males and 59 females; mean age, 62.30 ± 9.93 years) with T2DM, without (n = 48; T2DM group 1) and with (n = 39; T2DM group 2) cornea fluorescein staining, as well as 51 age- and sex-matched healthy subjects (18 males and 33 females; mean age, 61.53 ± 10.15 years). Ocular Surface Disease Index scores, Schirmer Ι test, tear meniscus height, the first breakup of tear film occurrence (NIKBUT-first), and the average time of all breakup incidents (NIKBUT-average) values were significantly lower for the T2DM groups than for the healthy group. The corneal sensations of all cornea positions in the T2DM groups were significantly different from the control group. The HbA1c in the T2DM groups showed a negative correlation with central BEC density (R = 0.348, P = .015; R = 0.91, P = .001); there was no correlation of HbA1c with BEC density in the control group. The BEC density, the area of BEC, SBN, and LC density of T2DM group 1 and T2DM group 2 were significantly different compared with the control group in all corneal positions (P < .001). The BEC density of T2DM group 2 was significantly different from T2DM group 1 in the central (P = .044) and inferior (P = .013) zones. The area of BEC in T2DM group 2 was significantly different from T2DM group 1 in inferior zone (P = .014) and other corneal positions showed was no significant difference (P > .05). The SBN density of T2DM group 2 was not significantly different from T2DM group 1 in all corneal positions (P > .05). The LC density of T2DM group 2 was significantly different from T2DM group 1 in the central (P = .006) and inferior (P = .006) zones. Although the LC density in the T2DM groups showed no significant difference in all corneal zones (P > .05), the LC density in the central zone was significantly lower compared with the peripheral zone in the control group (P = .001). The central ECs in the 3 groups were not significantly different (P > .05).LC induced an immune-mediated contribution to corneal nerve damage and may influence the early stages of BEC proliferation and differentiation in T2DM. BEC density was the reliable index for evaluating the early condition of diabetic corneal epitheliopathy. The BEC density of the central and inferior corneal zones was more sensitive.

Corneal microstructural changes in nerve fiber, endothelial and epithelial density after cataract surgery in patients with diabetes mellitus.

The aim of this study was to analyze microstructural corneal changes following phacoemulsification of cataract with intraocular lens insertion in diabetes mellitus (DM). Prospective study of consecutive patients undergoing phacoemulsification with intraocular lens insertion, over a period of 6 months. Age, gender, serum glycosylated hemoglobin A1c levels, and effective phacoemulsification time were recorded. Anterior segment optical coherence tomography and corneal in vivo confocal microscopy were performed preoperatively and 1-month postoperatively. Subbasal nerve plexus (SBN) density, basal epithelial cell density, and endothelial cell density (ECD) were quantitatively analyzed. Twenty-eight patients with type 2 DM (71.2 ± 7.6 years) and 23 healthy controls (mean age, 74.4 ± 7.4 years) were recruited. Mean hemoglobin A1c level was 7.5% in patients with DM and 5.7% in the control group (P < 0.0001). A significant reduction in SBN density was noted postoperatively in both DM (P < 0.0001) and non-DM groups (P < 0.0001). Patients with DM had a lower mean SBN density compared with non-DM group, before (P < 0.0001) and after surgery (P < 0.0001). Longer effective phacoemulsification time correlated with a greater decrease in ECD postoperatively in the whole cohort (P < 0.0001), and in the control (P = 0.002) and DM (P = 0.039) groups independently. There was no significant difference in preoperative ECD between the DM group (2254 +/- 426 cells/mm(2)) and non-DM group (2384 +/- 438 cells/mm(2); P = 0.2). [corrected]. Subbasal nerve density is reduced after cataract surgery in patients with and without DM. However, lower initial SBN density in patients with DM may predispose them to develop diabetic keratopathy. DM does not predispose to greater endothelial loss following phacoemulsification.

In VivoConfocal Microscopy Analysis of Corneal Microstructural Changes in Neurosurgically-Induced Neurotrophic Keratitis

<i>In Vivo</i>Confocal Microscopy Analysis of Corneal Microstructural Changes in Neurosurgically-Induced Neurotrophic Keratitis

Change in corneal microstructure with rigid gas permeable contact lens use following collagen cross-linking: an in vivo confocal microscopy study

AimTo study corneal microstructural changes with use of rigid gas permeable contact lenses (CLs) in keratoconus patients following collagen cross-linking (CXL).MethodsIn a prospective, non-randomised, comparative case series, keratoconus patients with...

Evaluation of Corneal Microstructure in Keratoconus: A Confocal Microscopy Study

To compare the corneal microstructure in patients with manifest keratoconus (KCN), subclinical KCN, and topographically normal relatives of patients with KCN and in healthy controls. Prospective and cross-sectional study. We enrolled 145 subjects in the study. The participants were divided into 4 groups, based on clinical and topographical evaluation: the manifest KCN group (n = 30), the subclinical KCN group (n = 32), the KCN relatives group (n = 53), and the control group (n = 30). Corneal microstructure was assessed by corneal in vivo confocal microscopy in all of the individuals. Mean outcome measures were basal epithelial cell density, endothelial cell density, anterior keratocyte density, posterior keratocyte density, sub-basal nerve density, sub-basal nerve diameter, and stromal nerve diameter. The mean basal epithelial cell density, endothelial cell density, and sub-basal nerve diameter were not significantly different among the 4 groups (P = 0.057, P = 0.592, and P = 0.393, respectively). The mean anterior and posterior stromal keratocyte densities were significantly lower in the manifest group, in the subclinical group, and in the relatives group when compared with the control group (for both parameters; P < 0.001, P < 0.001, and P< 0.001, respectively). The mean stromal nerve diameter in the manifest group, subclinical group, and relatives group was significantly higher than in the control group (P = 0.001, P = 0.049, and P = 0.004, respectively). The anterior and posterior stromal keratocyte densities were statistically lower and stromal nerve diameter was statistically higher in patients with manifest KCN, subclinical KCN, and topographically normal KCN relatives compared with controls. Confocal microscopy may be useful for the determination of early corneal microstructural changes before manifestation of typical or subtle topographic signs.

In vivo confocal microscopy of climatic droplet keratopathy

We describe the corneal microstructural changes in a patient with spheroidal degeneration using in vivo confocal microscopy. Multiple hypo‐ and hyper‐reflective spherical lesions were observed in the anterior corneal stroma and Bowman's layer ranging from 45 to 220 μm in size. The corneal epithelium, posterior stroma and endothelium were otherwise unaffected. In vivo confocal microscopy demonstrates good correlation with excised histological samples in climatic droplet keratopathy. It provides a non‐invasive technique to examine the living cornea for degenerative disease and acts as a bridge between clinical and laboratory observations.

In vivo laser confocal microscopy findings in patients with map-dot-fingerprint (epithelial basement membrane) dystrophy

Background:The purpose of this study was to investigate pathological changes of the corneal cell layer in patients with map-dot-fingerprint (epithelial basement membrane) dystrophy by in vivo laser corneal confocal microscopy.Methods:Two patients were evaluated using a cornea-specific in vivo laser scanning confocal microscope (Heidelberg Retina Tomograph 2 Rostock Cornea Module, HRT 2-RCM). The affected corneal areas of both patients were examined. Image analysis was performed to identify corneal epithelial and stromal deposits correlated with this dystrophy.Results:Variously shaped (linear, multilaminar, curvilinear, ring-shape, geographic) highly reflective materials were observed in the “map” area, mainly in the basal epithelial cell layer. In “fingerprint” lesions, multiple linear and curvilinear hyporeflective lines were observed. Additionally, in the affected corneas, infiltration of possible Langerhans cells and other inflammatory cells was observed as highly reflective Langerhans cell-like or dot images. Finally, needle-shaped materials were observed in one patient.Conclusion:HRT 2-RCM laser confocal microscopy is capable of identifying corneal microstructural changes related to map-dot-fingerprint corneal dystrophy in vivo. The technique may be useful in elucidating the pathogenesis and natural course of map-dot-fingerprint corneal dystrophy and other similar basement membrane abnormalities.

In Vivo Laser Confocal Microscopy Findings of Thygeson Superficial Punctate Keratitis

We looked for microstructural corneal characteristics of Thygeson superficial punctate keratitis (TSPK) in an in vivo investigation using laser scanning confocal microscopy. Five patients (3 men and 2 women; mean age, 51.8 years) with clinically diagnosed TSPK were enrolled in this study. All patients were examined by slit-lamp biomicroscopy and in vivo laser confocal microscopy. Deposits in selected confocal images of all corneal layers were evaluated qualitatively for shape and degree of light reflection. The most characteristic finding was aggregates of highly reflective deposits with a starburst-like appearance that corresponded with epithelial punctate lesions identified by slit-lamp biomicroscopy; the aggregates were sporadically observed in all cases at the superficial and basal epithelial cell layers. Subepithelial haze was observed in all cases. Langerhans cells were also sporadically observed in all cases at the basal epithelial layer. Bowman layer abnormalities were observed in 3 of 5 cases; all these patients had a long history of TSPK (eg, more than 1 year). In addition, the 3 patients had highly reflective, tiny, needle-shaped materials in the corneal stroma. In vivo laser confocal microscopy is capable of identifying characteristic corneal microstructural changes related to TSPK with a higher resolution than is available with slit-lamp biomicroscopy. It may also be a valuable tool for further research to elucidate both pathogenesis and the natural course of TSPK.

In Vivo Laser Confocal Microscopy Findings and Mutational Analysis for Schnyder's Crystalline Corneal Dystrophy

To identify any mutation of the UbiA prenyltransferase domain-containing protein 1 (UBIAD1) gene in Japanese patients with Schnyder's crystalline corneal dystrophy (SCCD) and to investigate in vivo microstructural phenotype and genotype correlations using laser scanning confocal microscopy (Heidelberg Retina Tomograph 2 Rostock Cornea Module; Heidelberg Engineering GmbH, Dossenheim, Germany). Small, comparative case series. Three patients from 3 pedigrees (3 males) with clinically diagnosed SCCD and their relatives (2 males, 1 female) participated in this study. All participants were examined genetically and by slit-lamp biomicroscopy and in vivo laser confocal microscopy. Genomic DNA from the patients and 100 unrelated healthy volunteers (200 chromosomes) was isolated from blood samples and used for mutation screening of the UBIAD1 gene. Selected confocal images of corneal layers were evaluated qualitatively for shape and degree of light reflection of deposits. Novel mutations in the UBIAD1 gene (Y174C, K181R, and N233H) were identified. Additionally, cosegregation of the mutation (Y174C) and SCCD was confirmed in 1 pedigree, indicating that the mutation of the UBIAD1 gene is causative for SCCD. The 3 mutations were absent in all 200 control chromosomes. In vivo laser confocal microscopy demonstrated subepithelial highly reflective crystals in 4 cases; the shapes of the crystals were needle-shaped (3 cases) or rectangular (1 case). A phenotype and genotype correlation was demonstrated in 1 pedigree, and phenotypic heterogeneity (SCCD with or without crystals caused by a same mutation of Y174C in the UBIAD1 gene) also was demonstrated in 1 pedigree. Nonsynonymous novel mutations in the UBIAD1 gene were detected in 3 unrelated Japanese pedigrees with SCCD, confirming the genetic heterogeneity of this disorder. In vivo laser confocal microscopy is capable of identifying characteristic corneal microstructural changes related to genetically mapped SCCD with high resolution, and phenotypic heterogeneity was presented. Further confocal and mutational analysis using a larger number of patients with SCCD is required to elucidate in vivo microstructural phenotype and genotype correlations. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

2008 Sir Norman McAlister Gregg Lecture: 150 years of practical observations on the conical cornea – what have we learned?

The first detailed descriptions of keratoconus were published exactly 150 years ago in the original work of Dr John Nottingham, bringing a degree of clarity to a previously confusing clinical phenomenon--further supported by observations of other contemporaries in the field such as Sir William Bowman. However, it would be another 100 years before knowledge of keratoconus would grow substantially; indeed, our current level of understanding is primarily a result of extensive clinical and laboratory research conducted over the last 50 years--particularly based upon the enormous technological advances of the last two decades. Large clinical studies have confirmed that keratoconus is a non-inflammatory corneal disease with central or paracentral corneal thinning, which exhibits progressive corneal steepening and protrusion that typically results in increasing regular and thereafter irregular astigmatism. Ultimately, disease progression may lead to corneal scarring, corneal hydrops and loss of best spectacle-corrected visual acuity. Although visual rehabilitation may be effected by expert contact lens fitting, 20% of subjects may require corneal transplantation. This Gregg lecture provides a highly referenced, wide-ranging overview of both historical and contemporary aspects of keratoconus, including diagnostic, phenotypic and prognostic factors revealed by large clinical studies, critical diagnostic advances enabled by Placido and slit-scanning computerized corneal topography, the emerging roles of higher order aberration wave-front analysis and corneal hysteresis in delineating early and subclinical keratoconus, inheritance and genetic predisposition to keratoconus, corneal microstructural changes unveiled by in vivo confocal microscopy, unifying theories to explain associations between keratoconus, atopy, eye rubbing and keratocyte apoptosis, and surgical options for keratoconus, such as corneal transplantation, intrastromal ring segments, collagen cross-linking and keratocyte transplantation. However, 150 years along the path our knowledge of keratoconus remains incomplete, but technological advances should enable us to put together the final pieces of the jigsaw in the foreseeable future.

In Vivo Laser Confocal Microscopic Findings of Corneal Stromal Dystrophies

To investigate in vivo laser confocal microscopic findings of genetically mapped corneal stromal dystrophies and their relationship to histopathologic findings. Seven patients with Avellino corneal dystrophy, 2 patients with lattice corneal dystrophy, and 2 patients with macular corneal dystrophy were examined genetically and using slitlamp biomicroscopy and in vivo laser confocal microscopy. Corneal specimens obtained after surgery in selected patients were histopathologically studied. In Avellino corneal dystrophy (Arg124His mutation of human transforming growth factor beta-induced gene [TGFBI]), highly reflective granular materials with irregular edges were observed in the superficial stroma. In lattice corneal dystrophy (Arg124Cys and Leu527Arg mutations of TGFBI), highly reflective branching filaments of variable width were observed in the stroma. In macular corneal dystrophy (Ala217Thr mutation of the carbohydrate sulfotransferase gene [CHST6]), homogeneous reflective materials with dark striaelike images were observed throughout the stroma. All confocal findings correlated well with histopathologic findings. In vivo laser confocal microscopy is capable of high-resolution visualization of characteristic corneal microstructural changes related to 3 types of genetically mapped corneal stromal dystrophies. The use of laser confocal microscopy may be valuable in the differential diagnosis of corneal stromal dystrophies, especially when diagnosis is otherwise uncertain.