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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 3  |  Issue : 1  |  Page : 19

Corneal dystrophies: A decade of experience in a reference center in Bogotá, Colombia


1 Department of Cornea, Fundación Oftalmológica Nacional; Universidad del Rosario, School of Human Sciences, Bogotá, Colombia
2 Universidad del Rosario, School of Human Sciences; Fundación Oftalmológica Nacional, Bogotá, Colombia

Date of Submission25-Apr-2021
Date of Acceptance19-May-2021
Date of Web Publication18-Jun-2021

Correspondence Address:
Dr. Matilde Mora
Calle 50 # 13-50, Bogotá
Colombia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pajo.pajo_91_21

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  Abstract 


Purpose: To describe sociodemographic findings, frequency, and clinical characteristics of patients with corneal dystrophy who consulted an ophthalmologic national reference center in Bogotá-Colombia in 10 years.
Methods: Observational, descriptive case series study was carried out. The information was obtained from reviewing medical records of patients who consulted the cornea service at an ophthalmologic national reference center in Bogotá-Colombia between 2008 and 2018. The diagnosis of corneal dystrophy was done according to the International Committee for Corneal Dystrophies classification, as well as the currently accepted specific name of the dystrophy. The type of dystrophy, clinical, diagnostic findings, sociodemographic characteristics, and type of treatment were evaluated.
Results: A total of 151 eyes of 79 patients were analyzed; 68.3% of subjects were female. The mean age was 57.6 ± 18.9 years, with a range between 2 and 95 years. The median best-corrected visual acuity (BCVA) in all the groups at diagnosis was 0.30 LogMAR (interquartile range 0.5) or 20/40 Snellen. Lattice dystrophy type 1 and its variants had the worse BCVA. Fuchs' dystrophy (FD) was the most frequently identified. Regarding treatment, 80.1% (n = 121) did not require any, and 11.9% (n = 18) had a corneal transplant. Thirteen underwent penetrating keratoplasty. Of those, two had a clinical diagnosis of TGFB1 dystrophy, three of stromal dystrophy, and eight of endothelial dystrophy. DSAEK was performed in 5 eyes four had endothelial dystrophy and one had unclassified dystrophy.
Conclusions: Adults and females were the most affected groups. FD was the most frequent and unclassified dystrophies were the second most frequently diagnosed. This highlights the importance of complementary studies such as optical coherence tomography of the anterior segment and genetic markers which are not currently universally available in our healthcare system.
Ethical considerations: This study was approved by the Institutional Ethics Committee and was conducted in accordance with the principles of the Declaration of Helsinki.

Keywords: Colombia, corneal dystrophy, corneal endothelial cell loss, corneal opacity, Latin America


How to cite this article:
Mora M, Mejia ME, Martinez-Ceballos MA, Roca D. Corneal dystrophies: A decade of experience in a reference center in Bogotá, Colombia. Pan Am J Ophthalmol 2021;3:19

How to cite this URL:
Mora M, Mejia ME, Martinez-Ceballos MA, Roca D. Corneal dystrophies: A decade of experience in a reference center in Bogotá, Colombia. Pan Am J Ophthalmol [serial online] 2021 [cited 2021 Nov 27];3:19. Available from: https://www.thepajo.org/text.asp?2021/3/1/19/318798




  Introduction Top


Corneal dystrophies (CD) are a group of hereditary diseases with heterogeneous genetic patterns (autosomal dominant, autosomal recessive, heritage with x-linked dominant or mitochondrial heritage). Frequently they present as a symmetric, bilateral condition with slow progression, CD does not have a relationship with environmental factors or systemic diseases.[1] The clinical presentation is characterized by diminished visual acuity, due to a progressive and irreversible opacification of the cornea or by endothelial dysfunction with loss of transparency of the corneal stroma due to edema.[2]

According to the World Health Organization (WHO), 4.2 million people develop a moderate to severe visual acuity compromise due to corneal opacities different from trachoma.[3] The prevalence of CD varies with the type of dystrophy and the geographic distribution. The CD prevalence in the United States from a 7 years national database was estimated to be 807 cases per million or 0.09%.[4] Local studies carried out in the United States, Canada, Europe, and Asia that used clinicopathological correlation, report CD prevalence between 3.1% and 14.8%.[5],[6]

There are few reports regarding the clinical characteristics and frequency of CD in the Colombian population. There is a report concerning the presence of gelatinous drop-like dystrophy in a consanguineous Colombian family, in which the genetic mutation was identified.[7]

The current classification used is the one proposed by the International Committee of Corneal Dystrophies (IC3D) of 2015.[2]

This case series describes the findings in the main CD in a referral center in Bogotá, Colombia. The results in our population and its characteristics provide valuable information for future research.


  Methods Top


An observational, descriptive, case series type study was carried out. We describe the type of CD diagnosed at Fundación Oftalmológica Nacional (FUNDONAL). This study was approved by the Institutional Ethics Committee and carried out in accordance with the principles of the Helsinki declaration.

The medical records from all the patients seen at the Cornea Service at FUNDONAL, Bogotá-Colombia, between January 2008 and December 2018, were reviewed. Medical records of patients with ICD-10 diagnosis (International Common Denomination) were chosen. Cornea specialists made the clinical diagnosis of CD. Patients with Bullous Pseudophakic Keratopathy, Keratoconus, Corneal Ectasias, and Leukoma of other origin were excluded, as well as those subjects with a history of ocular trauma or with incomplete data were excluded.

Data recollection (sociodemographic information, family history of CD, name of CD, IC3D classification, initial best-corrected visual acuity (BCVA), and treatment) was carried out by two independent authors (MEM and MAMC), the obtained data were recorded in a Microsoft Excel® database and verified by the Cornea specialist (MM). The statistical information was analyzed in the SPSS (R) software (IBM Corp. Released 2013. IBM SPSS Statistitcs for Windows, Version 22.0. Armonk, NY, USA: IBM Corp). The categorical variables were reported in percentage, and the quantitative variables with normal and nonnormal distribution were documented as mean and standard deviation, and median and interquartile range (IQR) respectively.


  Results Top


One hundred and fifty-one eyes of 79 patients were included. The median age was 60 years (IQR 22), with a range between 2 and 95 years, 97.4% were older than 20 years old. Females were the most prevalent (n = 54, 68.3%). Only four (5.1%) of the patients had a family history of CD and 124 (82.1%) were bilateral. [Table 1] shows the demographic characteristics and past medical history of the patients.
Table 1: Demographic characteristics and past medical history

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Type of dystrophies

Dystrophies were classified according to the specific diagnosis name and the IC3D classification. The most frequent dystrophy according to the specific name was Fuchs' dystrophy (FD) in 85 eyes (56.3%), followed by unclassified dystrophies in 31 eyes (20.5%), posterior polymorphous dystrophy (PPD) in 10 eyes (6.6%), lattice dystrophy type 1 and its variants in seven eyes (4.6%), Meesmann's dystrophy in six eyes (4%), Granular dystrophy type 1 and 2 in five eyes (3.3%), Fleck dystrophy in three eyes (2%), macular dystrophy in two eyes (1.3%), and epithelial basal membrane dystrophy in two eyes (1.3%) [Figure 1].
Figure 1: Clinicopathological correlation of cases. (a) Fuch's dystrophy, PAS stain showing papillary excrescences (guttae) on the posterior surface of Descemet's membrane. (b) Lattice dystrophy with Congo red stain and polarized filter, showing birefringent amyloid deposits and show dichroism. (c) Granular dystrophy with hyaline deposits on Masson's trichrome stain

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By the IC3D classification, Endothelial dystrophy was the most frequently found in 97 eyes (64.2%). This group presented with an average endothelial cell count of 1416.6 ± 827 cells per mm2. Unclassified dystrophy was the second most frequent with 22 eyes (14.6%), stromal dystrophy was found in fifteen eyes (9.9%), epithelial dystrophy in ten eyes (6.6%), and epithelial-stromal dystrophy (TGFB1) in seven eyes (4.6%).

Sex

Fifty-four patients (68.3%) were female and 25 (31.7%) were male. When analyzed by the IC3D classification we found females more affected [Table 2], but according to the specific diagnosis of CD, lattice dystrophy type 1 and its variants was the only one where male were predominant. Out of seven eyes diagnosed with it, 5 belong to males [Table 3].
Table 2: Sex distribution for each type of dystrophy according to the International Classification of Corneal Dystrophies

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Table 3: Sex distribution for each type of dystrophy according to the specific diagnosis of the corneal dystrophy

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Visual acuity

Initial BCVA was 0.30 LogMAR (Snellen 20/40) (IQR 0.50); and the BCVA in the last visit to cornea service was 0.40 LogMAR (Snellen 20/50) (IQR 0.40) for all patients in the charts reviewed.

The initial BCVA for each type of CD is shown in [Table 4] and [Table 5]. According to the IC3D classification and to the specific diagnosis. The worst BCVA for the IC3D classification was in the epithelial-stromal dystrophy group (TGF-B1 dystrophy), 1.0 LogMAR (Snellen 20/200) (IQR 1.46) [Table 4]. By specific diagnosis, the CD, lattice dystrophy type 1 and its variants had the worst initial BCVA of 2.00 LogMAR (Snellen 20/2000) (IQR 1,00) followed by granular dystrophy type 1 and type 2 with a median of BCVA 0.70 LogMAR (Snellen 20/100) (IQR 0,65), [Table 5].
Table 4: Visual acuity for each type of dystrophy according to International Classification of Corneal Dystrophies

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Table 5: Visual acuity for each type of dystrophy according to the specific name of the dystrophy

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Treatment

Of the 151 cases, 121 (80.1%) did not any require treatment and 15 (11.9%) underwent corneal transplant. Twelve cases (7.9%) were scheduled to have penetrating keratoplasty (PKP and were in the Eye Bank wait list. Of the transplanted patients, thirteen patients (8.6%) had PKP and five (3.3%) had endothelial keratoplasty (DSAEK) [Figure 2] and [Figure 3] describe the type of treatment for each CD according to IC3D and the specific diagnosis.
Figure 2: Treatment for each type of dystrophy according to the IC3D: International Classification of Corneal Dystrophies

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Figure 3: Treatment for each type of dystrophy according to the specific diagnosis of the CD

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Complementary studies

Six eyes (4%) had optical coherence tomography of anterior segment (OCT-AS) [Figure 4]. One patient had a granular dystrophy; the OCT-AS revealed granular deposits in the anterior half of the cornea in both eyes. Other patient of our case series had lattice dystrophy, the OCT-AS images show irregular corneal opacities and cystic lesions in the anterior stroma, disseminated intrastromal deposits and central corneal thinning in both eyes.
Figure 4: Optical coherence tomography of anterior segment of two study patients. (a) Granular dystrophy: Confluent hyperreflective granular deposits are seen in the anterior half of the cornea of both eyes. (b) Lattice dystrophy: An irregular cornea, opacities, and cystic lesions in the anterior stroma are observed in the upper and middle third of the visual axis with disseminated intrastromal deposits and central thinning in both eyes

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Four eyes (2.6%) had histopathological reports [Figure 1]. One patient had Fuch's dystrophy, PAS stain showing papillary excrescences (guttae) on the posterior surface of Descemet's membrane. Other case was of Lattice dystrophy with Congo red stain and polarized filter, showing birefringent amyloid deposits and show dichroism. Another case had Granular dystrophy with hyaline deposits on Masson's trichrome stain.


  Discussion Top


Considering the low prevalence of CD, its distribution in Caucasians,[1] and the few studies carried out in our population, it becomes relevant to describe the findings of CD in a reference center in Latin America.

The migratory flow to Colombia from the 16th century to the present has allowed a unique ethnic and racial diversity. Different foreign populations are represented. Spanish, African, Italian, French, German, Syrian-Lebanese, and Jewish standout, among others.[8] In this study, most of the patients seen with CD came from the Andean region not surprisingly given that Bogota, the country capital is in this area, where we are located. In second place is the Colombian Caribbean region, which has always been the gateway for foreigners. Since there is no particular evidence that suggests that CD has been common in any of the aboriginal people in our country, the genomic impact of these migrations is likely key to the development of these diseases in our current population.

FD was the most common CD in this study as occur with the worldwide literature.[9],[10],[11] This dystrophy is known to have a complex inheritance pattern and variable heterogeneity. The expressivity of the gene varies and its penetrance is incomplete.[2] Cases without known inheritance were the most common, from 51 patients we observed with FD, only 5 had a known familiar history of CD. FD has a high incidence in Caucasians, it has also been described in Asians and phenotypic and genotypic differences are found in different racial groups.[1] Research carried out in Colombia by Galvis et al., reports that FD is the third indication for keratoplasty, which could be seen as an indirect measure of its prevalence.[12] The presentation age in FD is around the fourth decade of life or later. The average age of presentation in our patients was 68 ± 10.1 years and females were the most affected.

Unclassified dystrophies ranked second in this case series. The most common finding was corneal haze, followed by central thick ropy-appearing lattice lines, flecks and specks up to the limbus. Several of these findings could be present in a single patient. These nonspecific characteristics may be present in FD, Lattice dystrophy type 1 and its variants, and Granular dystrophy.[13],[14],[15] On the other hand, we want to highlight the unilateral compromise of CD in our series, around 27 (17.9%) were unilateral, this clinical finding is also described in the international literature.[16],[17],[18],[19] Perhaps in the future with more advanced genetic and biochemistry techniques available, we will have more understanding of these conditions and new types of CD will be described.

PPD ranked third in frequency. This type of CD presents as an autosomal dominant inherited disease or can be isolated with unilateral involvement,[2] as was the case in 6 out of 10 of our patients. The onset of PPD is in childhood and it is usually asymptomatic, for this reason, the average age of patients at the first visit in this specific group is 57 ± 11.5 years. In these patients, PPD was found as an incidental finding in most cases.

When looking at visual acuity in our series, we found that lattice dystrophy type I and its variants and granular dystrophy presented with the worst initial BCVA, which is due to the pathophysiology of stromal dystrophies. Although these CD primarily affect the stroma, over time, they often extend into the anterior corneal layers and some can affect Descemet's membrane and the endothelium. Classically, stromal CD have been classified based on their phenotypic appearance in the slit lamp.[2] The morbidity associated with stromal CD varies widely. If there is the progressive accumulation of deposits on the cornea, the cornea may either lose its clarity or may have uneven elevations of the surface that can induce astigmatism resulting in decreased vision. When stromal dystrophies affect the anterior cornea, abnormal epithelial adherence can lead to painful erosions. In granular CD type 2 (GCD2), corneal deposits appear as granular lesions, linear lesions, and diffuse haze. Hong Seok Kim et al. indicated that linear lesions associated with GCD2 do not produce significant decreases in visual acuity, while diffuse haze leads to a more significant negative impact in vision.[20]

The therapeutic options for CD are superficial keratectomy, PKP, and phototherapeutic keratectomy which is associated with relatively early recurrence.[21] PKP has been considered the standard treatment in the management of CD.[22] In this case series, most of the patients were under observation, reflecting their good visual acuity on presentation.

Of the surgically treated ones, stromal and endothelial dystrophies required a higher number of corneal transplants, due to their visual impairment. Among stromal dystrophies (total of n = 15, 100%), four eyes (26.6%) required PKP and among endothelial dystrophies (total n = 97, 100%), eight eyes (8.2%) required PKP and four eyes (4.1%) DSAEK. PKP, was performed in FD in eight eyes, in four eyes with lattice dystrophy type 1 and its variants. None of the cases presented complications or adverse events. DSAEK was performed in four cases of Fuch's dystrophy (4.1%) with good results and grafts survival.

Currently, there are different surgical techniques that allow the replacement of the affected corneal layer, such as deep lamellar keratoplasty (DALK) and endothelial keratoplasties (DSAEK-DMEK).[23],[24] Endothelial keratoplasty, DSAEK (Descemet Stripping Automated Endothelial Keratoplasty), is indicated for corneal endothelial dysfunction.[25] Paz Valiñas L. et al. carried out a systematic review of the effectiveness and safety of DSAEK in patients with endothelial dysfunction. They mention several studies involving patients with FD including a 16 case series, reporting an improvement in BCVA with this technique with low astigmatism after DSAEK. The most frequent complications were dislocation or detachment of the graft and less commonly endothelial rejection.[23] Price et al., published the results of a 3-year follow-up of patients with FD treated with DSAEK technique versus PKP. The 3-year graft survival and endothelial cell loss were similar in both techniques. The DSAEK cohort experienced more endothelial cell loss in the 1st year, probably associated with surgical manipulation and graft trauma. However, in the following years, patients who underwent DSAEK technique showed a lower endothelial cell loss rate than the PPKP group resulting in a lower total cell loss with this selective corneal transplantation technique.[24] DSAEK also has other benefits such as minimal change in corneal surface topography resulting in a reduction in induced astigmatism, increased predictability in postoperative corneal power, decreased risk of neurotrophic ulcers due to protection of corneal innervation, and reduced rejection.[26]

OCT-AS is a noninvasive technique that captures high-resolution cross-sectional images, using infrared light that is reflected from tissue structures, measuring the backscattered light echo delay. OCT-AS shows corneal thickness, depth, extension, and distribution of the lesions and the amorphous material in the different corneal layers.[27] This is a diagnostic tool for the characterization of findings in the corneal tissue,[28] for example the presence of stromal hyperreflective material in the case of Granular dystrophies, as well as thinning and atrophy of the corneal epithelium in lattice dystrophy.[27] The information obtained by the OCT-AS is becoming relevant to the corneal specialist's therapeutic algorithm.

Study limitations are related to the lack of information in clinical records such as few genetic diagnoses, histopathological studies, and availability of OCT-AS since 2018 in FUNDONAL. Although, IC3D validates biomicroscopic clinical description as the gold standard for diagnosis.[2]


  Conclusions Top


This case series reports that CD are more prevalent in females and in the adult population. FD was the most frequent. On the other hand, unclassified dystrophies ranked second in frequency, which reflects the importance of genetic profile, complementary studies such as OCT-AS, and in cases that require keratoplasty, perform a histopathological study to achieve a proper characterization and possibly even describe new types of CD. The number of cases included in this case series is remarkable and allows us to describe the general panorama of CD in a Latin American population and could inspire future research in this field.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Galvis V, Tello A, Laiton AN, Salcedo SLL. Indications and techniques of corneal transplantation in a referral center in Colombia, South America (2012-2016). Int Ophthalmol 2019;39:1723-33.  Back to cited text no. 12
    
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Aldave AJ, Rayner SA, Kim BT, Prechanond A, Yellore VS. Unilateral lattice corneal dystrophy associated with the novel His572del mutation in the TGFBI gene. Mol Vis 2006;12:142-6.  Back to cited text no. 18
    
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Price MO, Gorovoy M, Benetz BA, Price FW Jr, Menegay HJ, Debanne SM, et al. Descemet's stripping automated endothelial keratoplasty outcomes compared with penetrating keratoplasty from the Cornea Donor Study. Ophthalmology 2010;117:438-44.  Back to cited text no. 24
    
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26.
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27.
Siebelmann S, Scholz P, Sonnenschein S, Bachmann B, Matthaei M, Cursiefen C, et al. Anterior segment optical coherence tomography for the diagnosis of corneal dystrophies according to the IC3D classification. Surv Ophthalmol 2018;63:365-80.  Back to cited text no. 27
    
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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